- Email: [email protected]
Neurotensin immunoreactivity and choline acetyltransferase activity in the cerebral cortex in Parkinson's disease
277
NEUROTENSIN IMMUNOREACTIVITY AND CHOLINE CEREBRAL CORTEX IN PARKINSON'S DISEASE
ACETYLTRANSFERASE
ACTIVITY
IN THE
J ALAN BIGGINS, ROBERT H PERRY, JOHN M CANDY, ELAINE K PERRY, CLIVE A BLOXHAM, MARY JOHNSON and JAMES A EDWARDSON, MRC Neuroendocrinology Unit and Department of Neuropathology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE. RIA analysis shows that neurotensin immunoreactivity is reduced in the cerebral cortex (frontal, temporal, parietal and occipital, Brodmann areas 10, 21, 40 and 19 respectively) of autopsy cases of Parkinson's disease both with and without cognitive impairment. The overall reduction of neurotensin immunoreactivity is greatest in the cognitively impaired group and this reduction reaches statistical significance in the frontal cortex. A significant reduction in choline acetyltransferase activity, and in some cases biochemical and histochemical acetylcholinesterase activity, was found in all cortical regions of the cognitively impaired group. In the mentally intact cases the choline acetyltransferase activity was at the lower end of the normal range. Contrary to current reports (I) the cognitively impaired group did not have Alzheimer's disease. These results are of interest since they indicate that putative neurotransmitter changes occur in the cerebral cortex in Parkinson's disease and are not restricted to subcortical regions. (I)
Marsden, C D (1982) Lancet ii,
1141-1147.
CHROMATOGRAPHIC ANALYSIS OF HYPOTHALAMIC CRF FROM SEVERAL SPECIES
J ALAN BIGGINS, A IAN SMITH, JOHN R McDERMOTT, ALEXANDER B KEITH, JOHN M CANDY, JOHN D TURNER and JAMES A EDWARDSON, MRC Neuroendocrinology Unit, Newcastle General Hospital and Department of Psychiatry, Newcastle University, Newcastle upon Tyne. Corticotrophin Releasing Factor (CRF) has been isolated and characterized from ovine hypothalamus and the structure reported to comprise a 41 residue peptide; the synthetic peptide shows identical hypophysiotropic potency with the endogenous peptide. Synthetic ovine CRF was used to produce specific antisera in rabbits, which has proven effective in both radiOimmunoassay (RIA) and immunocytochemical techniques (ICC). This antisera when used in RIA cross-reacts with rat, mouse and human CRF in hypothalamic extracts, producing respective tissue levels of 5.2, 6.1 and 11.1pmol/g compared to sheep hypothalamus of 39.7pmol/g. Subsequent chromatography of the tissue acid extracts using reverse phase HPLC and a 30 minute, 3-70% acetonitrile linear gradient containing 0.08% TFA, reveals the presence of a single major peak of immunoreactivity eluting in the region of the synthetic peptide standard. ICC of rat hypothalamic tissue indicates specific staining of both cell bodies and terminals after pre-treatment with colchicine, but specific staining has not yet been observed in post mortem human fixed material. A close relationship has been established between rat CRF which has an 83% sequence homology with ovine CRF; it is likely that both mouse and human CRF will show comparable levels of sequence homology.
NEUROTENSIN IMMUNOREACTIVITY AND CHOLINE CEREBRAL CORTEX IN PARKINSON'S DISEASE
ACETYLTRANSFERASE
ACTIVITY
IN THE
J ALAN BIGGINS, ROBERT H PERRY, JOHN M CANDY, ELAINE K PERRY, CLIVE A BLOXHAM, MARY JOHNSON and JAMES A EDWARDSON, MRC Neuroendocrinology Unit and Department of Neuropathology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE. RIA analysis shows that neurotensin immunoreactivity is reduced in the cerebral cortex (frontal, temporal, parietal and occipital, Brodmann areas 10, 21, 40 and 19 respectively) of autopsy cases of Parkinson's disease both with and without cognitive impairment. The overall reduction of neurotensin immunoreactivity is greatest in the cognitively impaired group and this reduction reaches statistical significance in the frontal cortex. A significant reduction in choline acetyltransferase activity, and in some cases biochemical and histochemical acetylcholinesterase activity, was found in all cortical regions of the cognitively impaired group. In the mentally intact cases the choline acetyltransferase activity was at the lower end of the normal range. Contrary to current reports (I) the cognitively impaired group did not have Alzheimer's disease. These results are of interest since they indicate that putative neurotransmitter changes occur in the cerebral cortex in Parkinson's disease and are not restricted to subcortical regions. (I)
Marsden, C D (1982) Lancet ii,
1141-1147.
CHROMATOGRAPHIC ANALYSIS OF HYPOTHALAMIC CRF FROM SEVERAL SPECIES
J ALAN BIGGINS, A IAN SMITH, JOHN R McDERMOTT, ALEXANDER B KEITH, JOHN M CANDY, JOHN D TURNER and JAMES A EDWARDSON, MRC Neuroendocrinology Unit, Newcastle General Hospital and Department of Psychiatry, Newcastle University, Newcastle upon Tyne. Corticotrophin Releasing Factor (CRF) has been isolated and characterized from ovine hypothalamus and the structure reported to comprise a 41 residue peptide; the synthetic peptide shows identical hypophysiotropic potency with the endogenous peptide. Synthetic ovine CRF was used to produce specific antisera in rabbits, which has proven effective in both radiOimmunoassay (RIA) and immunocytochemical techniques (ICC). This antisera when used in RIA cross-reacts with rat, mouse and human CRF in hypothalamic extracts, producing respective tissue levels of 5.2, 6.1 and 11.1pmol/g compared to sheep hypothalamus of 39.7pmol/g. Subsequent chromatography of the tissue acid extracts using reverse phase HPLC and a 30 minute, 3-70% acetonitrile linear gradient containing 0.08% TFA, reveals the presence of a single major peak of immunoreactivity eluting in the region of the synthetic peptide standard. ICC of rat hypothalamic tissue indicates specific staining of both cell bodies and terminals after pre-treatment with colchicine, but specific staining has not yet been observed in post mortem human fixed material. A close relationship has been established between rat CRF which has an 83% sequence homology with ovine CRF; it is likely that both mouse and human CRF will show comparable levels of sequence homology.