Altered neuron-glia interactions in a low, chronic prenatal ethanol exposure.
Serotoninergic neurons, astrocytes and nitrergic system play an important role in central nervous system (CNS) development. These systems are altered in prenatal ethanol exposure (PEE) but ethanol (EtOH) effects may be very diverse under different conditions. In this study, we analyzed morphologically two serotoninergic mesencephalic nuclei and three prosencephalic areas of serotoninergic innervation in a model of pre- and postnatal low-ethanol exposure. Female Wistar rats were orally exposed to EtOH 6.6% (v/v), ad libitum, for 6 weeks before mating and during gestation and lactation while control group received water ad libitum. Twenty-day-old offspring (P21) brains were processed and immunoreactivity (IR) using antibodies against tryptophan hydroxylase (TPH), 5-HT, 5-HT transporter (5HTT), glial fibrillary acidic protein (GFAP), S-100B protein, 200-kDa neurofilaments (Nf-200) and neuronal nitric oxide synthase (nNOS) was evaluated. Dorsal and median raphe nucleus (DRN and MRN), hippocampus (Hipp), striatum (Strt) and frontal cortex (FCx) were studied by computer-assisted image analysis. Relative optical density (ROD) of TPH-IR, 5-HT-IR and nNOS-IR neurons; cell area of GFAP-IR astrocytes; relative area of 5HTT-IR fibers and Nf-200-IR were evaluated. TPH-IR was increased in DRN and MRN and 5-HT-IR was increased only in MRN. 5-HTT-IR fibers and ROD of S-100B-IR astrocytes were increased in the three prosencephalic areas while GFAP-IR astrocytes were hypertrophied only in Hipp and FCx. Nf-200 expression was increased in Hipp and Strt and morphologically altered in the FCx. ROD of nNOS-IR neurons was increased in Strt and FCx but was not detected in Hipp. We have also detected morphological changes resembling accelerated development and maturation, and early aging. Considering the evidences of a close 5-HT-astroglial-NO relationship during CNS development the differential response of the studied regions is an interesting result that could be due to different gradients of development in the studied areas and/or different responses of those areas to the effects of a low pre- and postnatal ethanol exposure.
Evrard
Sergio Gustavo
SG
Instituto de Biologi;a Celular y Neurociencias Prof. Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, (C1121ABG), Buenos Aires, Argentina.
Vega
Maite Duhalde
MD
Ramos
Alberto Javier
AJ
Tagliaferro
Patricia
P
Brusco
Alicia
A
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D016707:Tissue Fixation; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D009569:Nitric Oxide; D012701:Serotonin; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D014365:Tryptophan Hydroxylase