Ison JR, Allen PD. Pre- but not post-menopausal female CBA/CaJ mice show less prepulse inhibition than male mice of the same age. Behav Brain Res 185: 76-81

Department of Brain & Cognitive Sciences, University of Rochester, Rochester, NY 14627, USA.
Behavioural Brain Research (Impact Factor: 3.03). 01/2008; 185(2):76-81. DOI: 10.1016/j.bbr.2007.07.014
Source: PubMed


Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) has been reported to be weaker in females than males for both humans and rats. Although there are exceptions, on balance these data suggest that PPI is sensitive to sex-specific neurosteroids; in contrast, most studies with mice have not replicated this effect. We compared PPI for noise decrement prepulses (quiet gaps) in female CBA/CaJ mice at 3-8 months (pre-menopausal: n = 55) and 17-25 months of age (post-menopausal, n = 33) with similarly aged groups of males (n = 48, 35). Both PPI and ASR levels were significantly reduced in pre-menopausal females compared to young males, but did not differ between post-menopausal females and old males. The observed PPI decrement in young female mice compared to young males agrees with one previous report in young C57BL/6J mice as well as the majority of studies with human subjects and some strains of rats. The absence of a sex difference in PPI for old mice is consistent with the hypothesis that PPI is affected by reproductive hormones present at high levels only in pre-menopausal females. We note that this effect size for PPI is small, perhaps consistent with reports that the PPI decrement in females is restricted to certain times within the menstrual cycle in women and the estrous cycle in rats. The negative findings previously reported in the mouse can be attributed to the small effect size and to procedural differences, including stimulus conditions, and the different strains and ages of mice.

Download full-text


Available from: Paul D Allen, Dec 17, 2013
  • Source
    • "Thus decreased GluN2B subunit phosphorylation and possibly its activity in the hippocampus of young mice may be an attempt to prevent excitotoxicity, whereas increased GluN2B subunit phosphorylation in older mice may exacerbate excitotoxic events. Indeed, we demonstrate increased phosphorylated GluN2B subunits in the hippocampus of 15 month-old 3xTg-AD females, largely suggesting increased activity of GluN2B-containing NMDARs in postmenopausal animals, as female mice are considered to initiate menopause at 12–14 months of age (Ison and Allen, 2007). Gender differences in AD patients have been reported and the incidence of the disease appears to be higher in post-menopausal women than in age-matched men (Fratiglioni et al., 1997; Bonomo et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Early cognitive deficits in Alzheimer's disease (AD) have been related to deregulation of N-methyl-D-aspartate receptors (NMDARs) and synaptic dysfunction in response to amyloid-beta peptide. NMDARs anchorage to post-synaptic membrane depends in part on Src kinase, which is also implicated in NMDAR activation and actin cytoskeleton stabilization, two processes relevant for normal synaptic function. In this study we analysed the changes in GluN2B subunit phosphorylation and the levels of proteins involved in Src related signaling pathways linking the Tyr kinase to actin cytoskeleton polymerization, namely reelin, disabled-1 (Dab1) and cortactin, in hippocampal and cortical homogenates obtained from the triple transgenic mouse model of AD (3xTg-AD) that shows progression of pathology as a function of age versus age-matched wild-type mice. Moreover, we evaluated regional post-synaptic actin polymerization using phalloidin labelling in hippocampal slices. Young (3month-old) 3xTg-AD mice male hippocampus exhibited decreased GluN2B Tyr1472 phosphorylation and reduced Src activity. In the cortex, decreased Src activity correlated with reduced levels of reelin and Dab1, implicating changes in the reelin pathway. We also observed diminished phosphorylated Dab1 and cortactin protein levels in hippocampus and cortex of young 3xTg-AD male mice. Concordantly with the recognized role of these proteins in actin stabilization, we detected a significant decrease in post-synaptic F-actin in 3month-old 3xTg-AD male CA1 and CA3 hippocampal regions. These data suggest deregulated Src-dependent signaling pathways involving GluN2B-composed NMDARs and post-synaptic actin cytoskeleton depolymerization in the hippocampus in early stages of AD.
    Experimental Neurology 08/2014; 261. DOI:10.1016/j.expneurol.2014.07.023 · 4.70 Impact Factor
  • Source
    • "Within each test, for a given mouse, startle amplitudes were averaged across all trials of the same stimulus conditions. PPI was defined as fractional reduction of startle, i.e., 1 minus the ratio of startle amplitude with vs. without prepulse (see, e.g., Ison and Allen 2007). Thus a value of 0 means no effect of the prepulse, a value of 1 means complete inhibition of startle, and a negative value indicates prepulse facilitation of the startle response. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Perceptual abnormalities such as hyperacusis and tinnitus often occur following acoustic overexposure. Although such exposure can also result in permanent threshold elevation, some individuals with noise-induced hyperacusis or tinnitus show clinically normal thresholds. Recent work in animals has shown that a "neuropathic" noise exposure can cause immediate, permanent degeneration of the cochlear nerve despite complete threshold recovery and lack of hair cell damage (Kujawa and Liberman, 2009; Lin et al., 2011). Here, we ask whether this noise-induced primary neuronal degeneration results in abnormal auditory behavior, based on the acoustic startle response (ASR) and prepulse inhibition (PPI) of startle. Responses were measured in mice exposed either to a "neuropathic" noise or to a lower intensity, "non-neuropathic" noise, and in unexposed controls. Mice with cochlear neuropathy displayed hyper-responsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed control-like responses. Gap PPI tests, often used to assess tinnitus, revealed limited gap detection deficits in mice with cochlear neuropathy only for certain gap-startle latencies, inconsistent with the presence of tinnitus "filling in the gap". Despite significantly reduced wave 1 of the auditory brainstem response, representing cochlear nerve activity, later peaks were unchanged or enhanced, suggesting compensatory neural hyperactivity in the auditory brainstem. Considering the rapid post-exposure onset of both cochlear neuropathy and exaggerated startle-based behavior, the results suggest a role for cochlear primary neuronal degeneration, per se, in the central neural excitability that could underlie the generation of hyperacusis.
    Journal of Neurophysiology 02/2014; 111(3):552. DOI:10.1152/jn.00184.2013 · 2.89 Impact Factor
  • Source
    • "Furthermore, PPI varies in women according to the stage of the menstrual cycle, suggesting that variations in sex hormones can influence PPI (Swerdlow et al., 1997; Jovanovic et al., 2004). Sex differences in PPI have also been reported in Wistar rats and in mice (males > females; Lehmann et al., 1999; Ralph et al., 2001; Ison and Allen, 2007), and PPI varies across the estrus cycle in rats (Koch, 1998). Administration of estrogens and androgens can facilitate PPI (van den Buuse and Eikelis, 2001; Gogos and Van den Buuse, 2003), although little is known about the role of specific hormone receptors, including the AR, that may mediate these changes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Testosterone influences the hypothalamic-pituitary-adrenal axis, anxiety-related behavior, and sensorimotor gating in rodents, but little is known about the role of the androgen receptor (AR) in mediating these influences. We compared levels of the stress hormone corticosterone at baseline and following exposure to a novel object in an open field in wild type (wt) male and female rats, and male rats with the testicular feminization mutation (Tfm) of the AR, which disables its function. Basal corticosterone was equivalent in all groups, but exposure to a novel object in an open field elicited a greater increase in corticosterone in Tfm males and wt females than in wt males. Tfm males also showed increased behavioral indices of anxiety compared to wt males and females in the test. Analysis of the immediate early gene c-Fos expression after exposure to a novel object revealed greater activation in Tfm males than wt males in some regions (medial preoptic area) and lesser activation in others (dentate gyrus, posterodorsal medial amygdala). No differences were found in a measure of sensorimotor gating (prepulse inhibition of the acoustic startle response), although Tfm males had an increased acoustic startle response compared to wt males and females. These findings demonstrate that ARs play a role in regulating anxiety-related behaviors, as well as corticosterone responses and neural activation following exposure to a mild stressor in rats.
    Hormones and Behavior 07/2011; 60(4):380-8. DOI:10.1016/j.yhbeh.2011.07.008 · 4.63 Impact Factor
Show more