Intrastriatal 6-OHDA lesion in adult offspring of gestationally stressed dams

BAIER CARLOS JAVIER; PALLARES MARÍA EUGENIA; ADROVER EZEQUIELA; KATUNAR MARÍA ROSA; RAISMAN-VOZARI RITA; ANTONELLI MARTA CRISTINA

Washington DC

Congreso; 44th Annual Meeting of the Society of Neuroscience; 2014

Society for Neurosciences

It has been demonstrated that maternal disturbances in animal models can influence the offspring?s brain chemistry, endocrine function, emotionality, and learning ability,. Exposure to adverse events in early life can alter adult behaviors and neurochemical indicators of midbrain dopamine (DA) activity, suggesting that the development of the DA system is sensitive to disruption by brief exposure to early stressors. In humans, dysfunction of dopaminergic system is associated with development of several neurological disorders such as Parkinson?s disease (PD), schizophrenia, attention‐deficit hyperactivity disorder and depression. The pathological hallmark of PD is the relatively selective loss of DA neurons in the substantia nigra compacta (SNc) in the ventral midbrain with posterior loss of DA in the nigroestriatal system, and presence of cell bodies enriched in a‐synuclein aggregates. Oxidative stress and neuroinflammation participate in the pathogenesis of PD. The neurotoxin 6‐hydroxydopamine (6‐OHDA) is a classical and valuable model of PD in the rat. The aim of the present study was to investigate whether prenatal restrain stress increases the vulnerability of DA neurons to degenerate after striatal 6‐OHDA injection in the adulthood. We found that prenatally stressed offspring showed higher levels of cells expressing tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and that these cells were more susceptible to a neurochemical insult with 6‐hydroxydopamine (6‐OHDA) in adulthood. Moreover, prenatally stressed rats presented differences in terms of the number and asymmetry of neuronal nitric oxide synthase‐expressing cells in the VTA and nucleus accumbens, respectively. Similar to the results described for TH‐expressing cells, the nitrergic systems were differentially regulated after 6‐OHDA lesion in control and prenatally stressed rats. These results indicated that prenatal stress affects the dopaminergic and nitrergic systems in the mesolimbic pathway. In addition, we propose that the mesolimbic areas are more susceptible than the motor areas to a neurochemical insult during adult life.