title: Area-specific effects of brain-derived neurotrophic factor (BDNF) genetic ablation on various neuronal subtypes of the mouse brain.
abstract: The effects of brain-derived neurotrophic factor (BDNF) on the development of presynaptic terminals and of neuronal subtypes in various brain areas were studied in BDNF-knockout (BDNF-/-) mice at postnatal days 15-17. Western analysis revealed no changes in the overall amount of a variety of synaptic proteins in BDNF-/- mice as compared to wild type mice. In addition, the complex between the vesicular proteins, synaptophysin and synaptobrevin, as well as their respective homodimers were unaltered. Moreover, no changes in the density of neurons were found in, e.g., the CA3 region of the hippocampus and the nucleus nervi facialis of BDNF-/- mice. However, cholinergic cells were reduced by 20% in the medial septum of BDNF-/- mice associated with a decrease in the activity of choline acetyltransferase and protein levels of nerve growth factor in the hippocampus by 16% and 44%, respectively. In the striatum, however, the total number of cholinergic cells were comparable in both groups, although the activity of choline acetyltransferase was decreased by 46%. In GABAergic interneurons, the expression of neuropeptides in various brain areas was differentially affected by BDNF deletion as revealed by immunohistochemistry. In the hippocampus and cortex of BDNF-/- mice, the density of neuropeptide Y-, somatostatin-, and parvalbumin-immunoreactive cells was drastically reduced, whereas the density of calretinin-positive cells was increased. The extent of these changes in neuropeptide-containing cells varied among hippocampal subregions. In the striatum, only the density of parvalbumin-immunoreactive cells was decreased by approximately 45%. In conclusion, BDNF deficiency is accompanied by a differential dysregulation in the expression of neuropeptides and calcium-binding proteins in otherwise intact GABAergic and glutamatergic neurons in a region-specific manner.
authors.affiliation: Centre for Anatomy, Functional Cell Biology, Charité-Medical Faculty, Free University and Humboldt University, D-10115 Berlin, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Grosse
authors.forename: Susann
authors.initials: S
authors.lastname: Djalali
authors.forename: Dong Rui
authors.initials: DR
authors.lastname: Deng
authors.forename: Markus
authors.initials: M
authors.lastname: Höltje
authors.forename: Britta
authors.initials: B
authors.lastname: Hinz
authors.forename: Katharina
authors.initials: K
authors.lastname: Schwartzkopff
authors.forename: Marcel
authors.initials: M
authors.lastname: Cygon
authors.forename: Thomas
authors.initials: T
authors.lastname: Rothe
authors.forename: Thomas
authors.initials: T
authors.lastname: Stroh
authors.forename: Rainer
authors.initials: R
authors.lastname: Hellweg
authors.forename: Gudrun
authors.initials: G
authors.lastname: Ahnert-Hilger
authors.forename: Heide
authors.initials: H
authors.lastname: Hörtnag
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D064032:Calbindin 2; D002452:Cell Count / Q000379:methods; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000145:classification* / Q000166:cytology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D050683:R-SNARE Proteins; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D007527:Isoenzymes; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D010320:Parvalbumins; D050683:R-SNARE Proteins; D064030:S100 Calcium Binding Protein G; D016708:Synaptophysin; D013004:Somatostatin; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1