1,721,001 research outputs found
Loffredo V., Torromino G., Esposito F., Carboncino A., Cecere A., Mele A., De Leonibus E. "Sex regulates memory capacity"
No full textMemory Capacity (MC) is the number of information maintained in memory. MC is regulated by fronto-striatal dopamine circuit and hippocampus (HP).
Using a modified version of the object recognition task, the DOT/IOT, we have recently showed that adult naïve male mice could discriminate 3,4,6 but not 9 different objects after a 1 min or 24 hrs delay. Moreover, it has been reported that male mice use the HP, as well as humans, to solve the task (Sannino et al 2012, Olivito et al 2014; Sugita et al 2015).
To report sex differences influencing MC, we have challenged 3 months old mice (males and females) with the 6-DOT (highest memory load), testing them at different time points.
We have found that 3 months old female mice properly perform the 6-DOT when tested at 1 min delay (Short Term Memory, STM), but they are impaired when tested 24 hr later (Long Term Memory, LTM). Female mice properly perform the 6-IOT (lowest memory load) independently on the delay.
We hypothesized that the impairment in LTM could reflect sex regulated differences in the use of different neuronal circuits to solve the task. Therefore, we are performing c-fos immunohistochemical analysis as an index of stimuli-induced neuronal activation on the HP and the prefrontal cortex, at different time points after exposing the animals to the 6-DOT. Preliminary data show that female mice, differently from males, do not activate the HP.
Sex-regulated neuronal activation might be relevant to understand the higher impact of dementia in women as compared to men
Has the hippocampus really forgotten about space?
No full textSeveral lines of evidence, including the discovery of place cells, have contributed to the notion that the hippocampus serves primarily to navigate the environment, as a repository of spatial memories, like a drawer full of charts; and that in some species it has exapted on this original one an episodic memory function. We argue that recent evidence questions the primacy of space, and points at memory load, whether spatial or not, as the challenge that mammalian hippocampal circuitry has evolved to meet
Estrogen-dependent hippocampal wiring as a risk factor for age-related dementia in women
No full textDopamine, Alpha-Synuclein, and Mitochondrial Dysfunctions in Parkinsonian Eyes
No full textParkinson’s disease (PD) is characterized by motor dysfunctions including bradykinesia, tremor at rest and motor instability. These symptoms are associated with the progressive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta and projecting to the corpus striatum, and by accumulation of cytoplasmic inclusions mainly consisting of aggregated alpha-synuclein, called Lewy bodies. PD is a complex, multifactorial disorder and its pathogenesis involves multiple pathways and mechanisms such as α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Motor symptoms manifest when there is already an extensive dopamine denervation. There is therefore an urgent need for early biomarkers to apply disease-modifying therapeutic strategies. Visual defects and retinal abnormalities, including decreased visual acuity, abnormal spatial contrast sensitivity, color vision defects, or deficits in more complex visual tasks are present in the majority of PD patients. They are being considered for early diagnosis together with retinal imaging techniques are being considered as non-invasive biomarkers for PD. Dopaminergic cells can be found in the retina in a subpopulation of amacrine cells; however, the molecular mechanisms leading to visual deficits observed in PD patients are still largely unknown. This review provides a comprehensive analysis of the retinal abnormalities observed in PD patients and animal models and of the molecular mechanisms underlying neurodegeneration in parkinsonian eyes. We will review the role of α-synuclein aggregates in the retina pathology and/or in the onset of visual symptoms in PD suggesting that α-synuclein aggregates are harmful for the retina as well as for the brain. Moreover, we will summarize experimental evidence suggesting that the optic nerve pathology observed in PD resembles that seen in mitochondrial optic neuropathies highlighting the possible involvement of mitochondrial abnormalities in the development of PD visual defects. We finally propose that the eye may be considered as a complementary experimental model to identify possible novel disease’ pathways or to test novel therapeutic approaches for PD
Pharmacological evidence of the role of the dorsal striatum in spatial learning in mice.
No full textDistinct pattern of c-fos m-RNA expression after systemic and intra-accumbens amphetamine and MK-801.
No full textMirtazapine treatment in a young female mouse model of Rett syndrome identifies time windows for the rescue of early phenotypes
Full text linkRett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder, mainly caused by mutations in the MECP2 gene. Reduction in monoamine levels in RTT patients and mouse models suggested the possibility to rescue clinical phenotypes through antidepressants. Accordingly, we tested mirtazapine (MTZ), a noradrenergic and specific-serotonergic tetracyclic antidepressant (NaSSA). In previous studies, we showed high tolerability and significant positive effects of MTZ in male Mecp2(1m1.1Bird)-knock-out mice, adult female Mecp2tm1.1Bird-hetero-zygous (Mecp2(+/-)) mice, and adult female RTT patients. However, it remained to explore MTZ efficacy in female Mecp2(+/-)mice at young ages. As RTT-like phenotypes in young Mecp2(+/-)mice have been less investigated, we carried out a behavioural characterization to analyze Mecp2(+/-)mice in "early adolescence " (6 weeks) and "young adulthood " (11 weeks) and identified several progressive phenotypes. Then, we evaluated the effects of either a 15-or a 30-day MTZ treatment on body weight and impaired motor behaviours in 11-week-old Mecp2+/-mice. Finally, since defective cortical development is a hallmark of RTT, we performed a histological study on the maturation of perineuronal nets (PNNs) and parvalbuminergic (PV) neurons in the primary motor cortex. The 30 day MTZ treatment was more effective than the shorter 15-day treatment, leading to the significant rescue of body weight, hindlimb clasping and motor learning in the accelerating rotarod test. Behavioural improvement was associated with normalized PV immunoreactivity levels and PNN thickness. These results support the use of MTZ as a new potential treatment for adolescent girls affected by RTT and suggest a possible mechanism of action
Sensory-motor behavioral characterization of an animal model of Maroteaux-Lamy syndrome (or Mucopolysaccharidosis VI).
No full textSimilar Therapeutic Efficacy Between a Single Administration of Gene Therapy and Multiple Administrations of Recombinant Enzyme in a Mouse Model of Lysosomal Storage Disease.
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