Plasticity of basal ganglia neurocircuitries following perinatal asphyxia : effect of nicotinamide

• Published in: Experimental brain research 2007-06, Vol.180 (1), p.139-152
• Main Authors: KLAWITTER, Verena, MORALES, Paola, BUSTAMANTE, Diego, GOMEZ-URQUIJO, Sonia, HOKFELT, Tomas, HERRERA-MARSCHITZ, Mario
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Animals, Newborn; Asphyxia; Asphyxia - drug therapy; Asphyxia - pathology; Atrophy; Basal ganglia; Basal Ganglia - pathology; Biological and medical sciences; Cell body; Cell Count - methods; Cell viability; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Ethidium - analogs & derivatives; Ethidium - metabolism; Female; Fundamental and applied biological sciences. Psychology; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Hydroxylase; Immunocytochemistry; Juveniles; Medical sciences; Medicin och hälsovetenskap; N-Methyl-D-aspartic acid receptors; Neocortex; Neostriatum; Nerve Net - drug effects; Neurology; Neuronal Plasticity - drug effects; Neuroprotection; Niacinamide - therapeutic use; Nicotinamide; Nitric oxide; Nitric Oxide Synthase Type I - metabolism; Nitric-oxide synthase; Organ Culture Techniques; Pregnancy; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - metabolism; Substantia nigra; Suffocation; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; Uterus; Vertebrates: nervous system and sense organs; Vitamin B Complex - therapeutic use
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s00221-006-0842-7

The potential neuroprotection of nicotinamide on the consequences of perinatal asphyxia was investigated with triple organotypic cultures. Perinatal asphyxia was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Sibling caesarean-delivered pups were used as controls. Three days later tissue from substantia nigra, neostriatum and neocortex was dissected and placed on a coverslip. After a month, the cultures were processed for immunocytochemistry and phenotyped with markers against the NMDA receptor subunit NR1, tyrosine hydroxylase (TH), or neuronal nitric oxide synthase (nNOS). Some cultures were analysed for cell viability. Nicotinamide (0.8 mmol/kg, i.p.) or saline was administered to asphyxia-exposed and caesarean-delivered control pups 24, 48 and 72 h after birth. Perinatal asphyxia produced a decrease of cell viability in substantia nigra, but not in neostriatum or neocortex. Immunocytochemistry confirmed the vulnerability of the substantia nigra, demonstrating that there was a significant decrease in the number of NR1 and TH-positive (+) cells/mm2, as well as a decrease in the length of TH+ processes, suggesting neurite atrophy. In control cultures, many nNOS+ cells were seen, with different features, regional distribution and cell body sizes. Following perinatal asphyxia, there was an increase in the number of nNOS+ cells/mm2 in substantia nigra, versus a decrease in neostriatum including reduced neurite length, and no apparent changes in neocortex. The main effect of nicotinamide was seen in the neostriatum, preventing the asphyxia-induced decrease in the number of nNOS+ cells and neurite length. Nicotinamide also prevented the effect of perinatal asphyxia on TH-positive neurite length. The present results support the idea that nicotinamide can prevent the effects produced by a sustained energy-failure condition, as occurring during perinatal asphyxia.