Intrastrial 6-OHDA Lesion in adult offspring of gestationally stressed dams

BAIER, CJ; PALLARÉS, ME; ADROVER, E; ADROVER, E., KATUNAR, MR, PALLARES,ME, BAIER, CJ, MADSER, KK, WAAGEPETERSEN, HS, SCHOUSBOE, A, ANTONELLI, MC; RAISMAN-VOZARI, R; ANTONELLI, MC

Washington, DC

Simposio; Annual Meeting of the Society for Neuroscience; 2014

Society for Neuroscience (SFN)

It has been previously demonstrated in animal models, that maternal disturbances can influence the brain chemistry, endocrine function, emotionality and learning ability of the offspring. 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, dysfunctions of the dopaminergic system (DAergic) 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 DAergic neurons in the substantia nigra compacta (SNc) and, to a lesser extent, in the ventral midbrain with a loss of DA contents in the striatum and the presence of cell bodies enriched in -synuclein aggregates in the ventral mesencephalon. 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 rodents. The aim of the present study was to investigate whether prenatal restrain stress increases the vulnerability of DAergic neurons after striatal 6-OHDA injection in 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-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 indicate that prenatal stress affects both DAergic and nitrergic systems in the mesolimbic pathway. In addition, the results show that mesolimbic areas are more susceptible than motor areas to a neurotoxic insult during adult life in prenatally stressed animals.