PMID- 12357434 OWN - NLM STAT- MEDLINE DCOM- 20021107 LR - 20061115 IS - 0021-9967 (Print) IS - 0021-9967 (Linking) VI - 453 IP - 1 DP - 2002 Nov 4 TI - Cerebellar Golgi, Purkinje, and basket cells have reduced gamma-aminobutyric acid immunoreactivity in stargazer mutant mice. PG - 85-99 AB - The stargazer mutant mouse has characteristic ataxia and head-tossing traits coupled with a severe impairment in the acquisition of classical eye-blink conditioning (Qiao et al. [1996] J. Neurosci. 16:640-648; Qiao et al. [ 1998] J. Neurosci. 18:6990-6999). These phenotypes are thought to be cerebellar mediated and have been attributed to the specific reduction in brain-derived neurotrophic factor (BDNF). The granule cells in the cerebellum of the stargazer mouse exhibit a near-total and exclusive ablation of BDNF mRNA expression and a consequent defect in TrkB receptor signalling. To investigate whether the stargazer mutation and lack of availability of BDNF in the granule cells compromise the phenotype of the cerebellar inhibitory neurons, specifically their immunoreactivity for gamma-aminobutyric acid (GABA); the levels of GABA neurotransmitter expressed in Golgi, Purkinje, and basket cells; and the density of their synaptic contacts were compared in stargazer and wild-type controls using electron microscopy and quantitative immunogold labelling. The data presented in this study clearly show that, in the spontaneous ataxic mutant mouse stargazer, the cerebellar inhibitory neurons have significantly reduced levels of GABA immunoreactivity indicative of a significant decrease in their GABA content compared with wild-type controls. Furthermore, the density of inhibitory synapses between Golgi interneurons and granule cells and also between basket and Purkinje cells in stargazer mutants is reduced to approximately half that in wild-type controls. Whether this reduction in GABA content and inhibitory synapse density is directly attributable to the lack of BDNF in the cerebellum of the stargazer mutant is yet to be proved. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Richardson, Christine A AU - Richardson CA AD - Department of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom. FAU - Leitch, Beulah AU - Leitch B LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Comp Neurol JT - The Journal of comparative neurology JID - 0406041 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/deficiency/genetics MH - Cell Communication/genetics/physiology MH - Cerebellar Ataxia/genetics/metabolism MH - Cerebellum/*metabolism/*ultrastructure MH - Immunohistochemistry MH - Interneurons/*metabolism/ultrastructure MH - Mice MH - Mice, Neurologic Mutants MH - Microscopy, Electron MH - Purkinje Cells/*metabolism/ultrastructure MH - Synapses/genetics/*ultrastructure MH - gamma-Aminobutyric Acid/*biosynthesis/genetics EDAT- 2002/10/03 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/10/03 04:00 PHST- 2002/10/03 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/10/03 04:00 [entrez] AID - 10.1002/cne.10406 [doi] PST - ppublish SO - J Comp Neurol. 2002 Nov 4;453(1):85-99. doi: 10.1002/cne.10406.