title: NADPH-diaphorase-positive neurons in the human inferior colliculus: morphology, distribution and clinical implications.
abstract: Using the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reaction with nitroblue tetrazolium, we provided a detailed investigation of the distribution, dimensional characteristics and morphology of NADPH-d-positive neurons in the three main subdivisions of the human inferior colliculus (IC): central nucleus, pericentral nucleus, and external nucleus. In accordance with their perikaryal diameter, dendritic and axonal morphology, these neurons were categorized as large (averaging up to 45 μm in diameter), medium (20-30 µm), small (13-16 µm) and very small (7-10 µm). Their morphological differences could contribute to varying functionality and processing capacity. Our results support the hypothesis that large and medium NADPH-d-positive cells represent projection neurons, while the small cells correspond to interneurons. Heretofore, the very small NADPH-d-positive neurons have not been described in any species. Their functions-and if they are, indeed, the smallest neurons in the IC of humans-remain to be clarified. Owing to their location, we posit that they are interneurons that connect the large NADPH-d-positive neurons and thereby serve as an anatomical substrate for information exchange and processing before feeding forward to higher brain centers. Our results also suggest that the broad distribution of nitric oxide (NO) synthesis in the human IC is closely tied to the neuromodulatory action of NO on collicular neurotransmitters such as GABA and glutamate, and to calcium-binding proteins such as parvalbumin. A deeper understanding of the relationship between NADPH-d-positive fibers in all IC connections and their co-localization with other neurotransmitters and calcium-binding proteins will assist in better defining the function of NO in the context of its interplay with the cerebral cortex, the sequelae of the aging process and neurodegenerative disorders.
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431, Sofia, Bulgaria.
authors.forename: D
authors.initials: D
authors.lastname: Hinova-Palova
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431, Sofia, Bulgaria. landzhov_medac@abv.bg.
authors.forename: B
authors.initials: B
authors.lastname: Landzhov
authors.affiliation: Department of Chemistry, Biochemistry, Physiology and Pathophysiology, Sofia University "St. Kliment Ohridski", 1407, Sofia, Bulgaria.
authors.forename: E
authors.initials: E
authors.lastname: Dzhambazova
authors.affiliation: , P.O. Box 2316, Del Mar, CA, 92014, USA.
authors.forename: L
authors.identifier: http://orcid.org/0000-0003-1885-4285
authors.initials: L
authors.lastname: Edelstein
authors.affiliation: Department of Anatomy, Histology and Embryology, Medical University of Varna, 9002, Varna, Bulgaria.
authors.forename: M
authors.initials: M
authors.lastname: Minkov
authors.affiliation: Department of Oral and Maxillofacial Surgery, Medical University of Sofia, 1431, Sofia, Bulgaria.
authors.forename: K
authors.initials: K
authors.lastname: Fakih
authors.affiliation: Department of Anatomy, Histology and Embryology, Medical University of Varna, 9002, Varna, Bulgaria.
authors.forename: R
authors.initials: R
authors.lastname: Minkov
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431, Sofia, Bulgaria.
authors.forename: A
authors.initials: A
authors.lastname: Paloff
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431, Sofia, Bulgaria.
authors.forename: W
authors.initials: W
authors.lastname: Ovtscharoff
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007245:Inferior Colliculi / Q000166:cytology* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000032:analysis*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000032:analysis
chemical_list: D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase
keywords: Human; Inferior colliculus; NADPH-diaphorase; Nitric oxide; Presbycusis