Gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows

<p>Abstract</p> <p>Background</p> <p>The decline noticed in several fertility traits of dairy cattle over the past few decades is of major concern. Understanding of the genomic factors underlying fertility, which could have potential applications to improve fertility, is very limited. Here, we aimed to identify and study those genes that associated with a key fertility trait namely estrous behavior, among genes expressed in four bovine brain areas (hippocampus, amygdala, dorsal hypothalamus and ventral hypothalamus), either at the start of estrous cycle, or at mid cycle, or regardless of the phase of cycle.</p> <p>Results</p> <p>An average heat score was calculated for each of 28 primiparous cows in which estrous behavior was recorded for at least two consecutive estrous cycles starting from 30 days post-partum. Gene expression was then measured in brain tissue samples collected from these cows, 14 of which were sacrificed at the start of estrus and 14 around mid cycle. For each brain area, gene expression was modeled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model. Genes whose expression patterns showed significant linear or quadratic relationships with heat scores were identified. These included genes expected to be related to estrous behavior as they influence states like socio-sexual behavior, anxiety, stress and feeding motivation (<it>OXT, AVP, POMC, MCHR1</it>), but also genes whose association with estrous behavior is novel and warrants further investigation.</p> <p>Conclusions</p> <p>Several genes were identified whose expression levels in the bovine brain associated with the level of expression of estrous behavior. The genes <it>OXT </it>and <it>AVP </it>play major roles in regulating estrous behavior in dairy cows. Genes related to neurotransmission and neuronal plasticity are also involved in estrous regulation, with several genes and processes expressed in mid-cycle probably contributing to proper expression of estrous behavior in the next estrus. Studying these genes and the processes they control improves our understanding of the genomic regulation of estrous behavior expression.</p

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Modulating Sema3A signal with a L1 mimetic peptide is not sufficient to promote motor recovery and axon regeneration after spinal cord injury

We examined whether Sema3A, which is upregulated at the site of spinal cord injury, exerts a direct effect on axons. We used ASNKL peptide that prevents specifically the inhibitory effect of Sema3A on L1/Neuropilin1 (Nrp1)-expressing axons. In the naïve mouse spinal cord, L1 is located on a subset of corticospinal axons, whereas Nrp1 is barely detectable. After contusion injury, Nrp1 is found on L1-negative immune cells, whereas its expression does not increase on severed axons. L1-expressing axons sprout extensively into the lesion site but no difference in axon density could be detected in the lesion area of mice treated with ASNKL. In agreement, these mice did not recover a better motor function than controls. Similarly, culture of neurons sensitive to ASNKL on cryosections of lesioned spinal cords revealed no effect of Sema3A. Our data indicate a limited direct effect of Sema3A on axonal growth at the site of a contusion injury, and suggest that alternative mechanisms underlie positive effects of Sema3A inhibition on motor recovery

Modulating Sema3A signal with a L1 mimetic peptide is not sufficient to promote motor recovery and axon regeneration after spinal cord injury

We examined whether Sema3A, which is upregulated at the site of spinal cord injury, exerts a direct effect on axons. We used ASNKL peptide that prevents specifically the inhibitory effect of Sema3A on L1/Neuropilin1 (Nrp1)-expressing axons. In the naïve mouse spinal cord, L1 is located on a subset of corticospinal axons, whereas Nrp1 is barely detectable. After contusion injury, Nrp1 is found on L1-negative immune cells, whereas its expression does not increase on severed axons. L1-expressing axons sprout extensively into the lesion site but no difference in axon density could be detected in the lesion area of mice treated with ASNKL. In agreement, these mice did not recover a better motor function than controls. Similarly, culture of neurons sensitive to ASNKL on cryosections of lesioned spinal cords revealed no effect of Sema3A. Our data indicate a limited direct effect of Sema3A on axonal growth at the site of a contusion injury, and suggest that alternative mechanisms underlie positive effects of Sema3A inhibition on motor recovery

Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A

Mutations in the L1 gene induce a spectrum of human neurological disorders due to abnormal development of several brain structures and fiber tracts. Among its binding partners, L1 immunoglobulin superfamily adhesion molecule (Ig CAM) associates with neuropilin-1 (NP-1) to form a semaphorin3A (Sema3A) receptor and soluble L1 converts Sema3A-induced axonal repulsion into attraction. Using L1 constructs containing missense pathological mutations, we show here that this reversion is initiated by a specific trans binding of L1 to NP-1, but not to L1 or other Ig CAMs, and leads to activation of the NO/cGMP pathway. We identified the L1–NP-1-binding site in a restricted sequence of L1 Ig domain 1, as a peptide derived from this region could reverse Sema3A repulsive effects. A pathological L1 missense mutation located in this sequence specifically disrupts both L1–NP-1 complex formation and Sema3A reversion, suggesting that the cross-talk between L1 and Sema3A might participate in human brain development