Sex Differences in the Brain: A Whole Body Perspective

Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other organs when considering neural sex differences is that we are likely to miss the fact that some brain sex differences develop to compensate for differences in the internal environment (i.e., because male and female brains operate in different bodies, sex differences are required to make output/function more similar in the two sexes). We also consider evidence that sex differences in sensory systems cause male and female brains to perceive different information about the world; the two sexes are also perceived by the world differently and therefore exposed to differences in experience via treatment by others. Although the topic of sex differences in the brain is often seen as much more emotionally charged than studies of sex differences in other organs, the dichotomy is largely false. By putting the brain firmly back in the body, sex differences in the brain are predictable and can be more completely understood

A quantitative method for microstructural analysis of myelinated axons in the injured rodent brain

MRI studies (e.g. using diffusion tensor imaging) revealed that injury to white matter tracts, as observed in for instance perinatal white matter injury and multiple sclerosis, leads to compromised microstructure of myelinated axonal tracts. Alterations in white matter microstructure are also present in a wide range of neurological disorders including autism-spectrum disorders, schizophrenia and ADHD. Whereas currently myelin quantity measures are often used in translational animal models of white matter disease, it can be an important valuable addition to study the microstructural organization of myelination patterns in greater detail. Here, we describe methods to extensively study the microstructure of cortical myelination by immunostaining for myelin. To validate these methods, we carefully analyzed the organization of myelinated axons running from the external capsule towards the outer layers of the cortex in three rodent models of neonatal brain injury and in an adult stroke model, that have all been associated with myelination impairments. This unique, relatively easy and sensitive methodology can be applied to study subtle differences in myelination patterns in animal models in which aberrations in myelination integrity are suspected. Importantly, the described methods can be applied to determine efficacy of novel experimental treatments on microstructural organization of cortical myelination

A quantitative method for microstructural analysis of myelinated axons in the injured rodent brain

MRI studies (e.g. using diffusion tensor imaging) revealed that injury to white matter tracts, as observed in for instance perinatal white matter injury and multiple sclerosis, leads to compromised microstructure of myelinated axonal tracts. Alterations in white matter microstructure are also present in a wide range of neurological disorders including autism-spectrum disorders, schizophrenia and ADHD. Whereas currently myelin quantity measures are often used in translational animal models of white matter disease, it can be an important valuable addition to study the microstructural organization of myelination patterns in greater detail. Here, we describe methods to extensively study the microstructure of cortical myelination by immunostaining for myelin. To validate these methods, we carefully analyzed the organization of myelinated axons running from the external capsule towards the outer layers of the cortex in three rodent models of neonatal brain injury and in an adult stroke model, that have all been associated with myelination impairments. This unique, relatively easy and sensitive methodology can be applied to study subtle differences in myelination patterns in animal models in which aberrations in myelination integrity are suspected. Importantly, the described methods can be applied to determine efficacy of novel experimental treatments on microstructural organization of cortical myelination