Hippocampal Dendritic Spines Modifications Induced by Perinatal Asphyxia

Abstract

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although Western Blot analysis also showed a slight decrease in β-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA.

Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

“…This discrepancy could be attributable to the following methodological differences between both studies: (a) In the study of Weitzdoerfer et al ( 2004a ), rats were submitted to 20 min of perinatal asphyxia instead of the 19 min used in the present study. It is well known that survival rate is drastically reduced and CNS damage increases with the duration of asphyxia (Loidl et al, 1994 ; Capani et al, 1997 , 2009 ; Saraceno et al, 2012 ); (b) Weitzdoerfer et al ( 2004a ) used female rats, while only male rats were used in the present study. There are well known sex differences in basal emotional reactivity in the EPM and other anxiety tests; (c) Weitzdoerfer et al ( 2004a ) assessed older asphyctic rats (24 months old) than those used in the present study (18 months old).…”

“…We employed a murine model of perinatal asphyxia originally developed by Bjelke et al ( 1991 ) and extensively described previously by our group (Capani et al, 1997 , 2001 , 2003 , 2009 ; Saraceno et al, 2010 , 2012 ; Galeano et al, 2011 , 2013 ) with minor modifications. On gestational day 22, pregnant rats ( n = 20) were left to deliver no more than two pups and were immediately euthanized by decapitation.…”

“…To study perinatal asphyxia in experimental settings, two murine models have been developed: the so-called “Levine-Rice” model which is induced in 7-day-old rats by unilateral carotid ligation followed by oxygen deprivation (Rice et al, 1981 ) and the model developed by Bjelke et al ( 1991 ) consisting in the immersion of the uterus horns still containing the fetuses, removed from ready-to-deliver rats, in a water bath at 37°C for 5–20 min (Capani et al, 2001 ). In the latter model, we have previously observed spatial reference and working memory impairments, increased astrogliosis and synaptic alterations in CA1 hippocampal area of adult rats (3–4 month-old) which had undergone 19 min of birth asphyxia (Saraceno et al, 2010 , 2012 ; Galeano et al, 2011 ).…”

Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia

“…Neonatal HI is associated to learning and memory impairments (Blanco et al 2015;Galeano et al 2011Galeano et al , 2015Takada et al 2016). Mainly, it has shown to cause several cellular and molecular modifications in the hippocampus, including astrogliosis and focal swelling, among others (Blanco et al 2015;Saraceno et al 2010Saraceno et al , 2012. The endogenous cannabinoids system (ECS) includes different enzymes responsible for endocannabinoid synthesis, transport and degradation, as well as endocannabinoids and endocannabinoid receptors (Ueda et al 2013).…”

Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia

“…In the present work we employed a model developed by Bjelke et al [4] that has been broadly employed [5][6][7][8][9][10][11]. Previous results show that PA can cause significant damage in different areas of the CNS, among them the striatum [4][5][6]10,11], such as astrogliosis, decreased phosphorylation of high and medium molecular weight neurofilaments, and synaptic alterations [6][7][8].…”