neuropeptide-y and Movement-Disorders

In this study, the motor deficit, cognition impairment and the vulnerability of different striatal interneurons to the 6-hydroxydopamine (6-OHDA)-induced excitotoxicity in unilateral medial forebrain bundle (MFB) lesion rats were analyzed by employing behavioral test, immunohistochemistry and Western blot methods. The apomorphine-induced rotation after MFB lesion was used as a valid criterion of motor deficit. The 6-OHDA damaged rats had limb rigidity with longer hang time compared to the controls in the grip strength test. Cognitive and mnemonic deficits of rats with unilateral MFB lesion were observed by the water maze task. The MFB lesion resulted in a significant loss of tyrosine hydroxylase (TH)+ cells in the contralateral striatum or substantia nigra. After dopaminergic depletion, the numbers of calretinin (Cr)+ and choline acetyltransferase (ChAT)+ interneurons were notably reduced while these of neuropeptide Y (NPY)+ were markedly increased in the striatum. No noticeable change in the number of parvalbumin (Parv)+ interneurons was found in 6-OHDA rats. In addition, the fiber densities for each individual interneuron were increased after 6-OHDA treatment, especially for the fiber densities of Parv+ and Cr+ interneurons. The Western blot analysis further confirmed the results described above. In conclusion, the MFB lesion model is suitable to mimic Parkinson's disease (PD), and our results are helpful for further understanding the underlying mechanism and the specific functions of various striatal interneurons in the pathological process of PD.

Topics: Adrenergic Agents; Animals; Apomorphine; Choline O-Acetyltransferase; Cognition Disorders; Corpus Striatum; Creatine; Interneurons; Male; Maze Learning; Medial Forebrain Bundle; Movement Disorders; Muscle Strength; Neuropeptide Y; Oxidopamine; Parvalbumins; Rats; Rats, Sprague-Dawley; Spatial Behavior; Tyrosine 3-Monooxygenase

A 47 year old man, one of a sibship affected by amyotrophic choreo-acanthocytosis was studied neuropathologically after some years of clinical observation. Besides the classic optical findings (neuronal loss, astrocytic gliosis and "status spongiosus" in the basal ganglia, namely in the caudate nucleus) a few MEnk+ and NPY+ neurons were observed immunocytochemically in the striatum. In the spinal cord also, while no neuronal loss was perceivable, both mild demyelination and interfibrillary astrocytic hyperplasia of the long tracts were present. On the other hand, microscopic findings of muscle and peripheral nerve showed no differences from what was previously intra-vitam appreciated in the same patient. The neuropathological and immunocytochemical findings of this case are discussed in relation to the differential diagnosis between amyotrophic choreo-acanthocytosis and Huntington's disease.

Topics: Atrophy; Blood Cell Count; Brain; Caudate Nucleus; Enkephalin, Methionine; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Male; Middle Aged; Movement Disorders; Muscles; Neuromuscular Diseases; Neuropeptide Y; Peripheral Nerves; Reflex, Stretch; Spinal Cord; Syndrome

Tissue concentrations of the neuropeptide somatostatin and the specific activities of glutamic acid decarboxylase (GAD) were measured in several regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. By the beginning of the fourth postnatal week, these animals exhibited clinical signs of a mixed spastic/dyskinetic syndrome with visual deficits. At the onset of neurological impairment, a significant decrease in GAD activity was detected in the occipital cortex (48-49%) and striatum (45-50%) when compared to either normal or weight-matched controls. At one subclinical stage of toxicity, decreased GAD activity was detected only in the occipital cortex (29-30%). Tissue levels of somatostatin did not change significantly in the occipital cortex of methylmercury-treated animals at any stage of the experiment. However, somatostatin levels in the striatum were significantly reduced at the onset of neurological impairment (55-57%) and at one subclinical stage of toxicity (49-54%). Immunohistochemistry for somatostatin- and neuropeptide Y-immunoreactive neurons confirmed a marked loss of cells in the dorsolateral region of the striatum with atrophy of the surviving neurons. In the cerebral cortex of methylmercury-treated animals the morphology and distribution of somatostatin-positive neurons appeared normal. In view of the reported co-localization of GAD and somatostatin in some non-pyramidal neurons of the cerebral cortex, these results indicate that methylmercury-induced lesions of the developing cerebral cortex involve a subpopulation of GABAergic neurons which are not co-localized with somatostatin. In the striatum, where GAD and somatostatin are not co-localized within the same neurons, methylmercury-induced lesions involve both GABAergic and somatostatin-positive neurons.

Topics: Aging; Animals; Cerebral Cortex; Corpus Striatum; Female; Glutamate Decarboxylase; Histocytochemistry; Immunohistochemistry; Interneurons; Male; Methylmercury Compounds; Movement Disorders; NADPH Dehydrogenase; Nerve Degeneration; Neuropeptide Y; Posture; Rats; Rats, Inbred Strains; Somatostatin