- Email: [email protected]
Cognitive decline in the streptozotocin-induced model of Alzheimer’s disease may be related to neuroinflammation and impairment in adult neurogenesis
P.5.f. Dementia and neurological disorders − Other (clinical) In conclusion, this study provides the first description of the subsynaptic distribution of AbPP and secretases in human brain cortical synapses and shows for the first time that the synaptic levels of AbPP decrease with increased age in the human cerebral cortex. This suggests a participation of the decreased levels of AbPP in the lower allostasis of synapses in the aged brain and their greater susceptibility to dysfunction characteristic of the early phases of AD and depression. References [1] Selkoe, D.J., 2002. Alzheimer’s disease is a synaptic failure. Science 298, 789–791. [2] Duman, R.S., Aghajanian, G.K., 2012. Synaptic dysfunction in depression: potential therapeutic targets. Science 338, 68−72. [3] Rebola, N., Pinheiro, P.C., Oliveira, C.R., Malva, J.O., Cunha, R.A., 2003. Subcellular localization of adenosine A1 receptors in nerve terminals and synapses of the rat hippocampus. Brain Res 987, 49−58. [4] Agostinho, P., Pli´assova, A., Oliveira, C.R., Cunha, R.A., 2015. Localization and trafficking of amyloid-b protein precursor and secretases: impact on Alzheimer’s disease. J Alzheimers Dis 45, 329–347.
P.5.e.002 Cognitive decline in the streptozotocininduced model of Alzheimer’s disease may be related to neuroinflammation and impairment in adult neurogenesis T.B. Bassani1 ° , M.M.F. Machado1 , J.M. Bonato2 , R.M.W. Oliveira2 , M.A.B.F. Vital1 1 Federal University of Paran´a, Department of Pharmacology, Curitiba, Brazil; 2 State University of Maring´a, Department of Pharmacology and Therapeutics, Maring´a, Brazil Background: Alzheimer’s disease (AD) is a neurodegenerative disorder of unknown etiology characterized by progressive cognitive decline. Neuropathologically, AD presents some features such as deposits of extracellular amyloid plaques, intracellular neurofibrillary tangles, neuronal death, loss of synapses and impairment of neurogenesis [1]. Dysfunction of adult neurogenesis may play a role in the etiopathology of Alzheimer’s disease, because neurogenesis is found to be impaired in patients with AD. In the adult brain, neurogenesis is essential for both learning and memory and also recovery from neuronal injury. Therefore, abnormalities in neurogenesis may contribute to the development of cognitive disorders such as AD [1]. Besides, neuroinflammation, which is known to be increased in the brains of AD patients, can negatively impact neurogenesis [2]. Objectives: The aim of this study was to evaluate the involvement of adult neurogenesis and neuroinflammation in the cognitive decline observed in the rat model of AD induced by intracerebroventricular (ICV) infusion of streptozotocin (STZ). Methods: Male wistar rats (n = 6−9) received through stereotaxic surgery a single bilateral ICV injection of STZ (3 mg/kg dissolved in sterile saline, 5 mL per injection site). Sham group received only sterile saline. At days 28−30 after surgery, the animals were tested for cognitive performance in the Object Location Task (OLT), Object Recognition Task (ORT) and Y maze. Right after behavioral tests, the rats were transcardially perfused for immunohistochemical analysis. Free floating immunohistochemistry of the lateral ventricles and hippocampus were performed to assess the expression of Doublecortin (DCX − newborn neurons marker), Iba-1 (ionized calcium binding adaptor molecule − microgliosis marker) and Glial Fibrillary Acidic Protein (GFAP − reactive astrocytes marker). Statistical analysis was performed using Student’s t-test and significance was set at P < 0.05. All
S663
procedures were approved by the Ethical Committee of Animal Experiment of Federal University of Paran´a (protocol 735). Results: The STZ group showed a significant deficit in shortterm recognition memory in the ORT (P < 0.01) and also in short-term spatial memory in the Y maze (P < 0.001) and OLT (P < 0.001) when compared to the sham group. These cognitive alterations were accompanied by a reduction in hippocampal and subventricular neurogenesis, which is demonstrated by a decrease in DCX-positive neurons in the dentate gyrus of hippocampus (P < 0.01) and in the lateral ventricles (P < 0.001) of the STZ group when compared to the sham group. Besides, there was a significant increase in the expression of GFAP- (P < 0.01) and Iba-1-positive cells (P < 0.05) in the CA3 region of hippocampus of the STZ group compared to the sham group. Conclusions: The STZ model of AD presented impairment in short-term recognition and spatial memories, which was associated with reduction in subventricular and hippocampal neurogenesis and also with astrogliosis and microgliosis in the hippocampus. Altogether, these results suggest that the cognitive decline observed in this animal model may be related to neuroinflammation and dysfunction in adult neurogenesis. References [1] Qu, Z-q, Zhou, Y., Zeng, Y-s, Lin, Y-k, Li, Y., Zhong, Z-q, Chan, W.Y., 2012. Protective Effects of a Rhodiola crenulata Extract and Salidroside on Hippocampal Neurogenesis against Streptozotocin-Induced Neural Injury in the Rat. PLoS ONE 7(1), e29641. [2] Wang, B., Jin, K., 2015. Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis 30, 355–365.
P.5.f. Dementia and neurological disorders − Other (clinical) P.5.f.001 Time course of the depressive mental states in Japanese patients with subacute myelo-optic neuropathy (SMON) T. Konishi1 ° , K. Hayashi2 , H. Sugiyama3 1 Gakusai Hospital, Neurology, Kyoto, Japan; 2 Utano National Hospital, Rehabiritation, Kyoto, Japan; 3 Utano National Hospital, Neurology, Kyoto, Japan Objectives: We tried to clarify the characteristics affecting the time course of the depressive mental states of Japanese SMON patients by the statistical analysis. Materials and Methods: The mental states were evaluated in eight male and eighteen female SMON patients (mean+SD age 76.9+8.0, range; 53−90) living in Kyoto prefecture using the Zung Self-rating Depression Scale (SDS) questionnaires for the evaluation of depressive mental states. Clinical symptoms of SMON were evaluated using medical checkup records established by the SMON Research Committee. In these 26 patients, SDS questionnaires and clinical evaluation were already done two to eleven (mean 6.5) years ago (the past periods). All SMON patients showed more than 24 points of mini-mental state examination at the present period and have not been treated with anti-depressants during this study. The study was approved by the ethics committee of Gakusai Hospital and each patient was given the informed consent. In the statistical analysis, the correlation coefficient parameters were calculated by the Pearson’s correlation coefficient and the changes of each item of SDS questionnaires were analyzed by student’s t test. In each analysis, less than 5% of p values were considered as having a significant difference in comparison.
P.5.e.002 Cognitive decline in the streptozotocininduced model of Alzheimer’s disease may be related to neuroinflammation and impairment in adult neurogenesis T.B. Bassani1 ° , M.M.F. Machado1 , J.M. Bonato2 , R.M.W. Oliveira2 , M.A.B.F. Vital1 1 Federal University of Paran´a, Department of Pharmacology, Curitiba, Brazil; 2 State University of Maring´a, Department of Pharmacology and Therapeutics, Maring´a, Brazil Background: Alzheimer’s disease (AD) is a neurodegenerative disorder of unknown etiology characterized by progressive cognitive decline. Neuropathologically, AD presents some features such as deposits of extracellular amyloid plaques, intracellular neurofibrillary tangles, neuronal death, loss of synapses and impairment of neurogenesis [1]. Dysfunction of adult neurogenesis may play a role in the etiopathology of Alzheimer’s disease, because neurogenesis is found to be impaired in patients with AD. In the adult brain, neurogenesis is essential for both learning and memory and also recovery from neuronal injury. Therefore, abnormalities in neurogenesis may contribute to the development of cognitive disorders such as AD [1]. Besides, neuroinflammation, which is known to be increased in the brains of AD patients, can negatively impact neurogenesis [2]. Objectives: The aim of this study was to evaluate the involvement of adult neurogenesis and neuroinflammation in the cognitive decline observed in the rat model of AD induced by intracerebroventricular (ICV) infusion of streptozotocin (STZ). Methods: Male wistar rats (n = 6−9) received through stereotaxic surgery a single bilateral ICV injection of STZ (3 mg/kg dissolved in sterile saline, 5 mL per injection site). Sham group received only sterile saline. At days 28−30 after surgery, the animals were tested for cognitive performance in the Object Location Task (OLT), Object Recognition Task (ORT) and Y maze. Right after behavioral tests, the rats were transcardially perfused for immunohistochemical analysis. Free floating immunohistochemistry of the lateral ventricles and hippocampus were performed to assess the expression of Doublecortin (DCX − newborn neurons marker), Iba-1 (ionized calcium binding adaptor molecule − microgliosis marker) and Glial Fibrillary Acidic Protein (GFAP − reactive astrocytes marker). Statistical analysis was performed using Student’s t-test and significance was set at P < 0.05. All
S663
procedures were approved by the Ethical Committee of Animal Experiment of Federal University of Paran´a (protocol 735). Results: The STZ group showed a significant deficit in shortterm recognition memory in the ORT (P < 0.01) and also in short-term spatial memory in the Y maze (P < 0.001) and OLT (P < 0.001) when compared to the sham group. These cognitive alterations were accompanied by a reduction in hippocampal and subventricular neurogenesis, which is demonstrated by a decrease in DCX-positive neurons in the dentate gyrus of hippocampus (P < 0.01) and in the lateral ventricles (P < 0.001) of the STZ group when compared to the sham group. Besides, there was a significant increase in the expression of GFAP- (P < 0.01) and Iba-1-positive cells (P < 0.05) in the CA3 region of hippocampus of the STZ group compared to the sham group. Conclusions: The STZ model of AD presented impairment in short-term recognition and spatial memories, which was associated with reduction in subventricular and hippocampal neurogenesis and also with astrogliosis and microgliosis in the hippocampus. Altogether, these results suggest that the cognitive decline observed in this animal model may be related to neuroinflammation and dysfunction in adult neurogenesis. References [1] Qu, Z-q, Zhou, Y., Zeng, Y-s, Lin, Y-k, Li, Y., Zhong, Z-q, Chan, W.Y., 2012. Protective Effects of a Rhodiola crenulata Extract and Salidroside on Hippocampal Neurogenesis against Streptozotocin-Induced Neural Injury in the Rat. PLoS ONE 7(1), e29641. [2] Wang, B., Jin, K., 2015. Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis 30, 355–365.
P.5.f. Dementia and neurological disorders − Other (clinical) P.5.f.001 Time course of the depressive mental states in Japanese patients with subacute myelo-optic neuropathy (SMON) T. Konishi1 ° , K. Hayashi2 , H. Sugiyama3 1 Gakusai Hospital, Neurology, Kyoto, Japan; 2 Utano National Hospital, Rehabiritation, Kyoto, Japan; 3 Utano National Hospital, Neurology, Kyoto, Japan Objectives: We tried to clarify the characteristics affecting the time course of the depressive mental states of Japanese SMON patients by the statistical analysis. Materials and Methods: The mental states were evaluated in eight male and eighteen female SMON patients (mean+SD age 76.9+8.0, range; 53−90) living in Kyoto prefecture using the Zung Self-rating Depression Scale (SDS) questionnaires for the evaluation of depressive mental states. Clinical symptoms of SMON were evaluated using medical checkup records established by the SMON Research Committee. In these 26 patients, SDS questionnaires and clinical evaluation were already done two to eleven (mean 6.5) years ago (the past periods). All SMON patients showed more than 24 points of mini-mental state examination at the present period and have not been treated with anti-depressants during this study. The study was approved by the ethics committee of Gakusai Hospital and each patient was given the informed consent. In the statistical analysis, the correlation coefficient parameters were calculated by the Pearson’s correlation coefficient and the changes of each item of SDS questionnaires were analyzed by student’s t test. In each analysis, less than 5% of p values were considered as having a significant difference in comparison.