- Email: [email protected]
Neuroanatomy
Journal of Chemical Neuroanatomy 10 (1996) 73-76
Book reviews
N-0-t-Y SekctedPapersof Walle J.H. Nauta Birkhatlser, Boston, 1993, ISBN: O-8176-3539-4 or 3-7643-3539-4 Neuroanatomy:SelectedPapersof Walle J.H. Nauta is a valuablecollectionof Walle Nauta’s most quoted andinfluentialpapers.They representa compendiumof anatomicalstudieson the a&rent ande&rent connections linking a variety of centralnervousstructuresto other str&ures. The book displaysthe extraordinary scopeof Walk Nauta’s career.The first five of the papersin this collectiondescribethe key stepsin the developmentof the silver impregnationtechnique- the leadingmethodfor unravellingthe complexlong tract circuitsin themamma&n brain for morethan20 years. It may be diflicult for youngneuroscientists now entering the field to imagine how profoundly this simple methodhelpedto changeour view of the brain. This method,more than any other beforeit, establishedthe basisfor all modernviews of complexsystemsin the centralnervoussystemand formed the foundationfor clinical neurologyand biological psychiatry.Oncethe methodhadbeenestablished, Nauta appliedit to a variety of stru&res. The paperson circuitry selectedfor this volume span the hypothalamus,hippocampus, brain stem,basalgangliaand cerebralcortex.It is difficult to overe&matethecontributionof thesepapersto the developmentof the scienceof neuroanatomy.Although some details inevitably have been revisedor reversedby more modern and physiologicalmethods, major fmdings have been sustainedand importantly thesepaperslaid out the strategies,conceptsandunderphings of moderncircuit tracing.Our recognitionof pitfalls in interpretationof anatomicaldataderivefrom critical discussionsin many of the seminalpaperscontainedin this volume.The seriesof papersnot only represent advancesin the anatomy of our time, they providea link to theearlyhistoricalattemptsat describing centralnervoussysteminterco~ecti~ity. Nauta was not only an impeccabkneuroanatomistbut a scholar with deepinterestandreverencefor thecontributionsof predemsorsin the diEcult and often unheraldedtask of describingthe brain’s wiring diagram. 0891-0618/96/315.00 0 1996 Elnevier Science B.V. All righta reserved SSDX 0891-0618(95)00096-P
Although Nauta is thought of as an anatomist’s anatomist,hewasalso a premierfunctionalist.He consistentlysoughtto assignphysiologicalsignificanceto the anatomicalfactswhich he uncoveredand by his example,encouraged othersto do so.His 1971chapteron ‘TheProblemof the Frontal Lobt: a Rainterpretation’, reprintedin this volume,represents his uniquetalentfor conceptualintegration.No onehasmadethe casemore eloquentlyfor the conceptthat functionsof the frontal lobe could be understoodin terms of anatomicalconnections,a themethat influencedme greatlyand one whichI havefollowedcloselyin my own research.This paper beginswith the clarion call: ‘the frontal lobe, despitedecadesof researchby physiologists,anatomists and clinicianshad remainedthe most mystifyingof the major subdivisionsof the cerebralcortex. Unlike any other of the great cerebralpromontories,the frontal lobeappearsnot to containa singlesub-fieldthat could beidentifiedwith any particularsensorymodality, and its entire expansemust accordingly be considered associationcortex’. Although we now understandthat the‘greatcerebralpromontory’doeshavesensoryspecific domains,theseringing statementsand the heuristic ideasespousedin this essayexcited a generationof neuroscientists to take up the challengeof uncovering thesecretsof thefrontal lobes.I am pleasedthat W.J.H. selectedthethreepaperson theprimatefrontal lobethat we did togetherto be among those included in this volume. In today’sfreneticworld of grantsand publications and sometimesunwarrantedclaims for priority, referenceto theNautapaperswill remindus of a scholarship of gentility, generosityand reverencefor historical precedence, and for thoughtfulintegrationof the past with thepresent.Nauta’scharminganduniquepersonal style is capturedin the introduction to the volume in which he graciouslyshareswith us his own personal view of his career,and of the obstacleswhich servedto increase his deep and enviable dedication to neuroanatomy.He was a role model for the many studentswho hadthe opportunityto work with him and who, without exception,count themselvesfortunateto havebeenhis studentor colleague.This volume is an historicaldocumentspanningthe originsandevolution
14
Book
of modern neuroanatomy and capturing a glimpse of the complex eloquent man who carried the banner for neuroanatomical investigation in our times. P.S. Goldman-Rakic
Section Neurobiology Yale University School of Medicine 333 Cedar Street, Room C-303 New Haven, CT 06520-8001, USA
. Alzkmer Disense: Therapeutic Strategies Ezio Giacobini and Robert Becker (Editors). Birkh&ser, Boston, 1994, ISBN O-8176-3757-5 or 3-7643-3757-5 This book is the latest of three in a series entitled ‘Advances in Alzheimer Disease Therapy’. It is based on presentations given at the ‘International Springfield Symposium on Advances in Alzheimer Therapy.’ The volume comprises of seventeen parts each containing between two to thirteen chapters. Moreover, the introduction contains two chapters, the first of which (by Giacobini) is an overview of the compounds that are discussed in the three volumes. Although I share the optimism of Dr. Giacobini that significant improvement will be made in the cholinomimetic therapy, I doubt that these improvements will come within two to three years. In the second chapter, Amaducci and Fratiglioni deal with the epidemiology of Alxheimers Disease (AD) and its impact on the treatment. The following XVII parts consist of single or multiauthored chapters. The first part is devoted to the neuropathologic and genetic basis of AD treatment. The amyloid cascade hypothesis implies that deposition of the amyloid B-protein is the causative agent of AD pathology and that neurofibrillary pathology, cell loss and dementia follow. Wisniewski and Wegiel indicate that study of the cells that are engaged in amyloid fibril formation (microglia, perivascular cells and myocytes) should be of highest priority in the development of therapeutic strategies to prevent and treat AD. In this respect, they emphasize that drugs affecting &protein amyloidogenesis and b-protein Iibrillogenesis are two areas that should be of high priority in research and development of treatment of AD. Hardy and Duff review the recent advances in understanding the disease and point out some of the problems and deficiences with the cascade hypothesis. The mechanism of Alzheimer neurofibrillary degeneration and a strategy to inhibit this type of degeneration is described by Iqbal and Grundke Iqbal. Olfactory function is severely compromised in the early stages of Alzheimers disease. Struble et al. suggest that using olfactory testing for diagnostic aid in AD may identify early changes. Miklossy describe the presence of spirochetes in the
reviews
blood, cerebrospinal fluid and brain of 14 AD cases. The characterization of spirochetes found in AD is important since it would enable one to develop serological tests for early detection of the infection. An implication of the observation of Miklossy would be that an appropriate antibiotic treatment could stop the progress of dementia or prevent it. Therapeutic strategies to arrest production and processing of amyloid are discussed in part II. Although no drugs are presented that arrest production and processing of amyloid, several suggestions to study amyloid precursor protein (APP) biogenesis and turnover as well as &A4 production and aggregation in cell free systems and cell culture models are presented. In part III, the choline&z system of human brain is discussed. Mesulam describes the localization as well as the source of butyryl cholinesterase (BChE) in human brain. He suggests that the high density of BChE positive glia in AD brains may play a permissive or causative role in the neuropathology of AD. Soreq et al. establish transgenic models for overexpressing human cholinesterases in cholinergic synapses of Xenopus laevis tadpoles and mice in order to study the role of choline@ neurotransmission in regulating synaptic structure and function. Sihnan et al. describe elegantly the structurefunction relationships in the binding of reversible inhibitors in the active-site gorge of acetylcholinesterase. Taken together, these studies indicate that acetycholinesterase inhibition by eptastigmine is associated with cognitive and clinical improvement. Hupenine-A, a novel anticholinesterase inhibitor, is suggested as a promising candidate for clinical development as a second generation of anticholinesterase in the treatment of AD by Tang et al. From in vitro and in vivo studies in animals, Emmerling et al. predict that CI-1002, a novel inhibitor of acetyl cholinesterase and muscarinic receptors will produce fewer peripheral side effects than other anticholinesterases and should improve patient compliance with treatment. In the next six chapters, the preclinical and/or clinical effects of several anticholinesterases including SDZ ENA 713, MDL 713, 745, galanthamine, velnacrine and tacrine are discussed by several authors. Part IV concludes with two chapters on the preclinical and clinical aspects of second and third generation cholinesterase inhibitors by Giacobini and Caudra, and Becker et al. The first authors have confirmed that central AChE inhibition and ACh levels are not necessarily correlated and report that individual inhibitors affect aminergic systems in different ways. The last authors describe the pharmacology and clinical efficacy of metrifonate. They emphasize the importance of monitoring patients for side effects which might be apparent after months of treatment during long clinical trials. Moreover, they plead to all who are investigating these drugs to undertake a thorough characterization of any patient who shows idiosyncratic responses to these drugs.
Book reviews
N-0-t-Y SekctedPapersof Walle J.H. Nauta Birkhatlser, Boston, 1993, ISBN: O-8176-3539-4 or 3-7643-3539-4 Neuroanatomy:SelectedPapersof Walle J.H. Nauta is a valuablecollectionof Walle Nauta’s most quoted andinfluentialpapers.They representa compendiumof anatomicalstudieson the a&rent ande&rent connections linking a variety of centralnervousstructuresto other str&ures. The book displaysthe extraordinary scopeof Walk Nauta’s career.The first five of the papersin this collectiondescribethe key stepsin the developmentof the silver impregnationtechnique- the leadingmethodfor unravellingthe complexlong tract circuitsin themamma&n brain for morethan20 years. It may be diflicult for youngneuroscientists now entering the field to imagine how profoundly this simple methodhelpedto changeour view of the brain. This method,more than any other beforeit, establishedthe basisfor all modernviews of complexsystemsin the centralnervoussystemand formed the foundationfor clinical neurologyand biological psychiatry.Oncethe methodhadbeenestablished, Nauta appliedit to a variety of stru&res. The paperson circuitry selectedfor this volume span the hypothalamus,hippocampus, brain stem,basalgangliaand cerebralcortex.It is difficult to overe&matethecontributionof thesepapersto the developmentof the scienceof neuroanatomy.Although some details inevitably have been revisedor reversedby more modern and physiologicalmethods, major fmdings have been sustainedand importantly thesepaperslaid out the strategies,conceptsandunderphings of moderncircuit tracing.Our recognitionof pitfalls in interpretationof anatomicaldataderivefrom critical discussionsin many of the seminalpaperscontainedin this volume.The seriesof papersnot only represent advancesin the anatomy of our time, they providea link to theearlyhistoricalattemptsat describing centralnervoussysteminterco~ecti~ity. Nauta was not only an impeccabkneuroanatomistbut a scholar with deepinterestandreverencefor thecontributionsof predemsorsin the diEcult and often unheraldedtask of describingthe brain’s wiring diagram. 0891-0618/96/315.00 0 1996 Elnevier Science B.V. All righta reserved SSDX 0891-0618(95)00096-P
Although Nauta is thought of as an anatomist’s anatomist,hewasalso a premierfunctionalist.He consistentlysoughtto assignphysiologicalsignificanceto the anatomicalfactswhich he uncoveredand by his example,encouraged othersto do so.His 1971chapteron ‘TheProblemof the Frontal Lobt: a Rainterpretation’, reprintedin this volume,represents his uniquetalentfor conceptualintegration.No onehasmadethe casemore eloquentlyfor the conceptthat functionsof the frontal lobe could be understoodin terms of anatomicalconnections,a themethat influencedme greatlyand one whichI havefollowedcloselyin my own research.This paper beginswith the clarion call: ‘the frontal lobe, despitedecadesof researchby physiologists,anatomists and clinicianshad remainedthe most mystifyingof the major subdivisionsof the cerebralcortex. Unlike any other of the great cerebralpromontories,the frontal lobeappearsnot to containa singlesub-fieldthat could beidentifiedwith any particularsensorymodality, and its entire expansemust accordingly be considered associationcortex’. Although we now understandthat the‘greatcerebralpromontory’doeshavesensoryspecific domains,theseringing statementsand the heuristic ideasespousedin this essayexcited a generationof neuroscientists to take up the challengeof uncovering thesecretsof thefrontal lobes.I am pleasedthat W.J.H. selectedthethreepaperson theprimatefrontal lobethat we did togetherto be among those included in this volume. In today’sfreneticworld of grantsand publications and sometimesunwarrantedclaims for priority, referenceto theNautapaperswill remindus of a scholarship of gentility, generosityand reverencefor historical precedence, and for thoughtfulintegrationof the past with thepresent.Nauta’scharminganduniquepersonal style is capturedin the introduction to the volume in which he graciouslyshareswith us his own personal view of his career,and of the obstacleswhich servedto increase his deep and enviable dedication to neuroanatomy.He was a role model for the many studentswho hadthe opportunityto work with him and who, without exception,count themselvesfortunateto havebeenhis studentor colleague.This volume is an historicaldocumentspanningthe originsandevolution
14
Book
of modern neuroanatomy and capturing a glimpse of the complex eloquent man who carried the banner for neuroanatomical investigation in our times. P.S. Goldman-Rakic
Section Neurobiology Yale University School of Medicine 333 Cedar Street, Room C-303 New Haven, CT 06520-8001, USA
. Alzkmer Disense: Therapeutic Strategies Ezio Giacobini and Robert Becker (Editors). Birkh&ser, Boston, 1994, ISBN O-8176-3757-5 or 3-7643-3757-5 This book is the latest of three in a series entitled ‘Advances in Alzheimer Disease Therapy’. It is based on presentations given at the ‘International Springfield Symposium on Advances in Alzheimer Therapy.’ The volume comprises of seventeen parts each containing between two to thirteen chapters. Moreover, the introduction contains two chapters, the first of which (by Giacobini) is an overview of the compounds that are discussed in the three volumes. Although I share the optimism of Dr. Giacobini that significant improvement will be made in the cholinomimetic therapy, I doubt that these improvements will come within two to three years. In the second chapter, Amaducci and Fratiglioni deal with the epidemiology of Alxheimers Disease (AD) and its impact on the treatment. The following XVII parts consist of single or multiauthored chapters. The first part is devoted to the neuropathologic and genetic basis of AD treatment. The amyloid cascade hypothesis implies that deposition of the amyloid B-protein is the causative agent of AD pathology and that neurofibrillary pathology, cell loss and dementia follow. Wisniewski and Wegiel indicate that study of the cells that are engaged in amyloid fibril formation (microglia, perivascular cells and myocytes) should be of highest priority in the development of therapeutic strategies to prevent and treat AD. In this respect, they emphasize that drugs affecting &protein amyloidogenesis and b-protein Iibrillogenesis are two areas that should be of high priority in research and development of treatment of AD. Hardy and Duff review the recent advances in understanding the disease and point out some of the problems and deficiences with the cascade hypothesis. The mechanism of Alzheimer neurofibrillary degeneration and a strategy to inhibit this type of degeneration is described by Iqbal and Grundke Iqbal. Olfactory function is severely compromised in the early stages of Alzheimers disease. Struble et al. suggest that using olfactory testing for diagnostic aid in AD may identify early changes. Miklossy describe the presence of spirochetes in the
reviews
blood, cerebrospinal fluid and brain of 14 AD cases. The characterization of spirochetes found in AD is important since it would enable one to develop serological tests for early detection of the infection. An implication of the observation of Miklossy would be that an appropriate antibiotic treatment could stop the progress of dementia or prevent it. Therapeutic strategies to arrest production and processing of amyloid are discussed in part II. Although no drugs are presented that arrest production and processing of amyloid, several suggestions to study amyloid precursor protein (APP) biogenesis and turnover as well as &A4 production and aggregation in cell free systems and cell culture models are presented. In part III, the choline&z system of human brain is discussed. Mesulam describes the localization as well as the source of butyryl cholinesterase (BChE) in human brain. He suggests that the high density of BChE positive glia in AD brains may play a permissive or causative role in the neuropathology of AD. Soreq et al. establish transgenic models for overexpressing human cholinesterases in cholinergic synapses of Xenopus laevis tadpoles and mice in order to study the role of choline@ neurotransmission in regulating synaptic structure and function. Sihnan et al. describe elegantly the structurefunction relationships in the binding of reversible inhibitors in the active-site gorge of acetylcholinesterase. Taken together, these studies indicate that acetycholinesterase inhibition by eptastigmine is associated with cognitive and clinical improvement. Hupenine-A, a novel anticholinesterase inhibitor, is suggested as a promising candidate for clinical development as a second generation of anticholinesterase in the treatment of AD by Tang et al. From in vitro and in vivo studies in animals, Emmerling et al. predict that CI-1002, a novel inhibitor of acetyl cholinesterase and muscarinic receptors will produce fewer peripheral side effects than other anticholinesterases and should improve patient compliance with treatment. In the next six chapters, the preclinical and/or clinical effects of several anticholinesterases including SDZ ENA 713, MDL 713, 745, galanthamine, velnacrine and tacrine are discussed by several authors. Part IV concludes with two chapters on the preclinical and clinical aspects of second and third generation cholinesterase inhibitors by Giacobini and Caudra, and Becker et al. The first authors have confirmed that central AChE inhibition and ACh levels are not necessarily correlated and report that individual inhibitors affect aminergic systems in different ways. The last authors describe the pharmacology and clinical efficacy of metrifonate. They emphasize the importance of monitoring patients for side effects which might be apparent after months of treatment during long clinical trials. Moreover, they plead to all who are investigating these drugs to undertake a thorough characterization of any patient who shows idiosyncratic responses to these drugs.