Neurogenesis of GABAergic cells in the retina of malnourished rats

Abstract

The present study investigated how prenatal protein malnutrition affects the neurogenesis of GABAergic cells in the retina. Rats were treated with a multi-deficient diet, with only 8% of protein that was administered during the gestational and suckling periods. Pregnant mothers and pups from malnourished and control (fed with 22% protein) groups received a single intra-peritoneal injection of [3H]-thymidine at six developmental ages, from E14 to PN4, and the pups were sacrificed at PN18. Eyes were enucleated and cryosections of the retina were double labeled for GABA-immunocytochemistry and for autoradiography. The percentage of double labeled cells, in the retinal inner nuclear and ganglion cell layers, was determined for both groups. Qualitative and quantitative results showed that double labeled cells [GABA+/thymidine+] were present since E14, when mitotic activity for GABAergic cells starts, in both GCL and INL layers. The peak rate of GABAergic cell generation was reached in control animals injected with [3H]-thymidine at E18 in both central and peripheral sectors of the retina, but only at E20 in the malnourished group. The generation of cells of GABA phenotype showed a significant delay in both layers of the retina in the malnourished group. At PN4, close to the age that GABAergic mitotic activity ends in the control group, double labeled cells were significantly higher in the malnourished group. Our data showed a delay in GABAergic cell generation in the malnourished group when compared to the control group that might result in significant functional consequences in the developing retina.

Retinal development impairment and degenerative alterations in adult rats subjected to post‐natal malnutrition

“…However, because a differential pattern of GABA release induced by EAA was observed in the malnourished retinas of adult rats, it was possible to hypothesize that further important alterations are triggered by malnutrition in retinal tissue. Although the malnourished adult rat retina showed the same GABA expression pattern compared to control rat retinas, the delay in the neurogenesis and ontogenesis of the GABAergic cell population caused by malnutrition (Almeida et al, 2005, 2001; Silveira et al, 2007) could have a functional impact on the establishment of retinal circuitry. Further analyses are necessary to clarify the reasons behind the differential effect of EAAs on GABA release in the malnourished retina.…”

“…The retinal tissue may suffer various deleterious effects of malnutrition, such as the delayed expression of acetylcholine, GABA and calcium‐binding proteins (Almeida et al, 2001) and the neurogenesis of retinal GABAergic cells (Almeida et al, 2001; Silveira et al, 2007). These alterations have been observed during development, but there are no data on the deleterious effects on adult retinal tissue after malnutrition during the postnatal development.…”

Intrauterine Programmierung von Störungen der Hirnfunktion im späteren Leben

“…Eine Mangelernährung und insbesondere eine proteinarme Ernährung führen bei Ratten ebenfalls über eine Störung der Neuroneogenese [215,216] zu strukturellen Störungen des Gehirns [203] sowie zu dauerhaften Störungen der neuronalen Erregbarkeit [217,218] und der Funktion von Neurotransmittersystemen [219][220][221] . Dabei sind die gleichen Neurotransmittersysteme betroffen, deren Funktion durch pränatal erhöhte Glukokortikoidspiegel dauerhaft beeinflusst wird (siehe oben).…”

Neurochemical phenotype and birthdating of specific cell populations in the chick retina

“…5). Birth dates of GABAergic neurons were also determined in the rat retina by using BrdU or thymidine as markers (Lee et al 1999, Silveira et al 2007. In both cases, the rate of GABAergic cell generation peaked at E18 in both central and peripheral sectors of the retina, and displayed a homogenous generation rate from E14 to PN4, ending after that.…”