Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis.

Background: Multiple sclerosis (MS) varies considerably in its incidence and progression in females and males. In spite of clinical evidence, relatively few studies have explored molecular mechanisms possibly involved in gender-related differences. The present study describes possible cellular- and molecular-involved markers which are differentially regulated in male and female rats and result in gender-dependent EAE evolution and progression.

Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis.

Aims: Recent data in mouse and rat demyelination models indicate that administration of thyroid hormone (TH) has a positive effect on the demyelination/remyelination balance. As axonal pathology has been recognized as an early neuropathological event in multiple sclerosis, and remyelination is considered a pre-eminent neuroprotective strategy, in this study we investigated whether TH administration improves nerve impulse propagation and protects axons.

Methods: We followed up the somatosensory evoked potentials (SEPs) in triiodothyronine (T3)-treated and untreated experimental allergic encephalomyelitis (EAE) Dark-Agouti female rats during the electrical stimulation of the tail nerve.

Triiodothyronine administration ameliorates the demyelination/remyelination ratio in a non-human primate model of multiple sclerosis by correcting tissue hypothyroidism.

Remyelination failure is a key landmark in chronic progression of multiple sclerosis (MS), the most diffuse demyelinating disease in human, but the reasons for this are still unknown. It has been shown that thyroid hormone administration in the rodent models of acute and chronic demyelinating diseases improved their clinical course, pathology and remyelination. In the present study, we translated this therapeutic attempt to experimental allergic encephalomyelitis (EAE) in the non-human primate Callithrix Jacchus (marmoset).

A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain.

Polychlorinated dibenzo-dioxins, furans and dioxin-like polychlorinated biphenyls are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues of animals and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a lipophilic endocrine-disrupting molecule that accumulates in adipose tissue, placenta and milk. polychlorinated biphenyls and TCDD are known to interfere with thyroid hormone metabolism and signaling in the developing brain.

Sex-dimorphic changes in neuroactive steroid levels after chronic experimental autoimmune encephalomyelitis.

Our previous observations have shown that neuroactive steroid levels in the brain are affected by acute experimental autoimmune encephalomyelitis (EAE) with sex and regional specificity (Giatti et al. 2010). To better understand the effect of EAE on neuroactive steroids, we have here assessed the levels of pregnenolone, progesterone and its derivatives (i.

Acute experimental autoimmune encephalomyelitis induces sex dimorphic changes in neuroactive steroid levels.

Incidence, progression and severity of the multiple sclerosis, an inflammatory, demyelinating disease of the central nervous system (CNS) are affected in a sex-depending way. Physiological situations characterized by changes in sex steroid plasma levels, such as menstrual cycle, menopause or pregnancy, affect the disease course, suggesting that these molecules might exert a role in this disease. In order to understand better this possible relationship, we have here assessed the levels of neuroactive steroids present in different CNS regions of male and female rats affected by acute experimental autoimmune encephalomyelitis (EAE).

Gabapentin treatment improves motor coordination in a mice model of progressive ataxia.

No causal treatment of ataxias is available at the moment, and so symptomatic and disease-modifying therapies are regarded as a reliable possibility for this complex group of movement disorders. In order to explore possible pharmacological strategies aimed at interfering with ataxia development or progression, we used HCN1-/- mice. Mice carrying the deletion of the gene encoding for the voltage-dependent K-channel (HCN1-/-) have a normal basic motor function, but impaired learning of the motor skills that enable mice to balance on the rotating rod.

Skin homeostasis during inflammation: a role for nerve growth factor.

The skin is a neuroendocrine immune organ in which many different molecules operate in autocrine-paracrine manner to guarantee tissue homeostatsis in physiological and pathophysiological conditions. In this paper we examined NGF and p75 receptor expression in the skin, during CFA induced inflammation, in a time-course study. We also examined cutaneus innervation and proliferation, by means of immunohistochemistry and quantitative image analysis, RT-PCR and Western blot.

Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease.

Hyperforin (Hyp) is an active compound contained in the extract of Hypericum perforatum, well known for its antidepressant activity. However, Hyp has been found to possess several other biological properties, including inhibitory effects on tumor invasion, angiogenesis, and inflammation. In this paper, we show that treatment with Hyp inhibited IFN-gamma production, with down-regulation of T-box (T-bet; marker of Th1 gene expression) and up-regulation of GATA-3 (marker gene of Th2) on IL-2/PHA-activated T cells.

Changes in brain cholinergic markers and spatial learning in old galanin-overexpressing mice.

The cholinergic forebrain system is involved in learning and memory, and its age-dependent decline correlates with a decrease in cognitive performance. Since the neuropeptide galanin participates in cholinergic neuron regulation, we have studied 19- to 23-month-old male mice overexpressing galanin under the platelet-derived growth factor B promoter (GalOE) and wild-type (WT) littermates by monitoring behavioral, neurochemical and morphological/histochemical parameters. In the Morris water maze test, old transgenic animals showed a significant impairment in escape latency in the hidden platform test compared to age-matched WT animals.

Endogenous stem and precursor cells for demyelinating diseases: an alternative for transplantation?

Remyelination can be very effective in human. However, this process ultimately fails in multiple sclerosis (MS). In this paper, we discuss the possibility of stimulating endogenous oligodendrocyte precursors to participate in remyelination in experimental models (rat and primate Callithrix jacchus) of MS through thyroid hormone (TH) administration.

A molecular study of hippocampus in dogs with convulsion during canine distemper virus encephalitis.

In this study, we have investigated the expression of the nuclear transcription factor (c-Fos, NFkB), growth factors (nerve growth factor--NGF, brain-derived neurotrophic factor--BDNF), peptides (enkephalin, galanin) and glutamate transporter (AA 504-523 rat EAAC1) in 6 dogs sacrificed immediately after seizure attack during encephalomyelitis due to canine distemper virus (CDV) (as assessed by clinical examination, RT-PCR and viral RNA detection either in blood or brain tissue and CDV immunohistochemistry in brain slices). In all these CDV affected dogs, the observed neurological signs included untreatable seizures, leading to cluster seizure activity and status epilepticus. In the inter-ictal phase abnormal mentation, postural and gait deficits and sometimes involuntary movements such as myoclonus were recorded.

Thyroid hormone and remyelination in adult central nervous system: a lesson from an inflammatory-demyelinating disease.

Re-myelination in the adult CNS has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that re-myelination is effective in multiple sclerosis (MS), the most diffuse demyelinating disease. Moreover, chronic disabilities in MS are believed to be due to remyelination failure and consequent neuron damage and degeneration.

Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats.

Clinical symptoms in multiple sclerosis include cognitive dysfunction. Difficulties in learning and remembering new information represent the most common cognitive deficit and are associated with a general and progressive brain pathology. Possible pathogenetic mechanisms for neuronal damage such as neuroprotective strategies are under active investigation also in experimental allergic encephalomyelitis, the most widely used experimental model for multiple sclerosis.

p75(NTR)-immunoreactivity in the subventricular zone of adult male rats: expression by cycling cells.

While the study of in vitro regulation of neural stem cell lineage from both embryonic and adult neurospheres is greatly advanced, much less is known about factors acting in situ for neural stem cell lineage in adult brain. We reported that neurotrophin low affinity receptor p75(NTR) is present in the subventricular zone (SVZ) in adult male rats. We then characterized co-distribution of markers associated with precursor cells (nestin and PSA-NCAM) with growth factor receptors (p75(NTR), trkA, EGFr) and proliferation-associated antigens (Ki67 and BrDU-uptake) in adult male rat by immunocytochemistry and confocal laser scan microscopy.

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease.

Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.

Stem cells and nervous tissue repair: from in vitro to in vivo.

Recent development in stem cell biology has indicated a new possible approach for the treatment of neurological diseases. However, in spite of tremendous hope generated, we are still on the way to understand if the use of stem cells to repair mature brain and spinal cord is a reliable possibility. In particular, we know very little on the in situ regulation of adult neural stem, and this also negatively impact on cell transplant possibilities.

Neural stem cells and cholinergic neurons: regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor.

Degenerative diseases represent a severe problem because of the very limited repair capability of the nervous system. To test the potential of using stem cells in the adult central nervous system as "brain-marrow" for repair purposes, several issues need to be clarified. We are exploring the possibility of influencing, in vivo, proliferation, migration, and phenotype lineage of stem cells in the brain of adult animals with selective neural lesions by exogenous administration (alone or in combination) of hormones, cytokines, and neurotrophins.