Elevated Glutamate and Glutamine Levels in the Cerebrospinal Fluid of Patients With Probable Alzheimer's Disease and Depression

Recent evidence suggests that Alzheimer's disease (AD) and depression share common mechanisms of pathogenesis. In particular, deregulation of glutamate-mediated excitatory signaling may play a role in brain dysfunction in both AD and depression. We have investigated levels of glutamate and its precursor glutamine in the cerebrospinal fluid (CSF) of patients with a diagnosis of probable AD or major depression compared to healthy controls and patients with hydrocephalus. Patients with probable AD or major depression showed significantly increased CSF levels of glutamate and glutamine compared to healthy controls or hydrocephalus patients. Furthermore, CSF glutamate and glutamine levels were inversely correlated to the amyloid tau index, a biomarker for AD. Results suggest that glutamate and glutamine should be further explored as potential CSF biomarkers for AD and depression

Age-related changes in prepulse inhibition of the startle response

IntroductionAcoustic prepulse inhibition of the startle response (PPI) is a phenomenon characterized by the reduction in the startle reflex caused by the presence of weak and brief stimulus before an intense and sudden stimulus (pulse). These phenomena can be observed in several species, but in humans it is commonly measured by the eyeblink using electromyography. PPI works as an operational measure of sensorimotor gating, which is the ability to suppress motor responses for sensory stimulus. Healthy aging is marked by several changes in neural processing, like inhibitory functioning decline. In this line, PPI measure can be a potential biomarker for changes related to the aging process.MethodsIn this research we aim to investigate if PPI is reduced with aging and if this reduction would be associated with cognitive functioning of older adults. To this aim, we compared PPI levels of older adults (over 60 years old) with PPI levels of young adults (from 18 to 28 years old).ResultsWith that, we found, significantly lower PPI level (F[1,25] = 7.44 p = 0.01) and lower startle amplitude startle amplitude: (U = 26.000 p = 0.001) in older adults than in young adults. However, we did not find differences in levels of habituation (T = −1.1 p = 0.28) and correlation between PPI and cognition within the sample of healthy older adults.DiscussionOur results demonstrate that aging is a factor that affects PPI and that it does not seem to predict cognition, however, future studies should explore the potential of using PPI for monitoring cognitive changes associated with techniques such as cognitive training

Blood Levels of Glutamate and Glutamine in Recent Onset and Chronic Schizophrenia

Converging evidence indicates that dysfunctions in glutamatergic neurotransmission and in the glutamate-glutamine cycle play a role in the pathophysiology of schizophrenia. Here, we investigated glutamate and glutamine levels in the blood of patients with recent onset schizophrenia or chronic schizophrenia compared to healthy controls. Compared with healthy controls, patients with recent onset schizophrenia showed increased glutamine/glutamate ratio, while patients with chronic schizophrenia showed decreased glutamine/glutamate ratio. Results indicate that circulating glutamate and glutamine levels exhibit a dual behavior in schizophrenia, with an increase of glutamine/glutamate ratio at the onset of schizophrenia followed by a decrease with progression of the disorder. Further studies are warranted to elucidate the mechanisms and consequences of changes in circulating glutamate and glutamine in schizophrenia

Potential and Challenges for the Clinical Use of d-Serine As a Cognitive Enhancer

After 25 years of its discovery in the rat brain, d-serine is a recognized modulator of synaptic plasticity and cognitive processes through its actions on the NMDA-glutamate receptor. Importantly, cognitive impairment is a core feature of conditions, such as schizophrenia, Alzheimer’s disease, depression, and aging, and is associated to disturbances in NMDA-glutamate receptors. The d-serine pathway has been associated with cognitive deficits and these conditions, and, for this reason, d-serine signaling is subject of intense research to probe its role in aiding diagnosis and therapy. Nevertheless, this has not resulted in new therapies being incorporated into clinical practice. Therefore, in this review we will address many questions that need to be solved by future studies, regarding d-serine pharmacokinetics, possible side effects, other strategies to modulate its levels, and combination with other therapies to increase its efficacy

Magnetic resonance imaging in drug discovery: lessons from disease areas.

Imaging technologies are presently receiving considerable attention in the pharmaceutical area owing to their potential to accelerate the drug discovery and development process. One of the principal imaging modalities is magnetic resonance imaging (MRI). The multiparametric nature of MRI enables anatomical, functional and even molecular information to be obtained non-invasively from intact organisms at high spatial resolution, thereby enabling a comprehensive characterization of a disease state and the corresponding drug intervention. The non-invasiveness of MRI strengthens the link between pre-clinical and clinical drug studies, making the technique attractive for pharmaceutical research

TNF-A Levels throughout the Critical Period for Experience-Dependent Plasticity in the Rat Primary Auditory Cortex

Tumor necrosis factor- alpha (TNF-α) is likely to play a role in brain plasticity. To determine whether TNF-α levels change throughout a critical period of experience-dependent brain plasticity, we assessed these levels in the primary auditory cortex of rats before, during and after the critical period (at postnatal day 7, postnatal day 12 and at adulthood, respectively). TNF-α levels in the auditory cortex increased from before to after a critical period of brain plasticity. We suggest that TNF-α may play a role in the brain plasticity that occurs in the auditory cortex

Manipulation of BDNF signaling during critical period affects the tonotopic organization, receptive fields and cortical representation of A1.

<p>(A, B, C) Tonotopic maps (left) of control, anti-BDNF, and BDNF groups; <i>x</i> = no tone-evoke responses; <i>circle inside polygon</i> = multi/flat-peaked sites. (Center) Distributions of tuning curves from illustrated map. The pair of joined lines represents the receptive field of each recorded site, and the apex indicates the threshold of activation of these sites. (Right) Representative receptive field from each displayed map (see number inside maps). (D) Receptive fields tuned to 7 kHz±0.3 octave were significantly increased in the BDNF group compared to control and anti-BDNF groups (F = 7.3, p<0.05, ANOVA). (E, F) The proportion of receptive fields tuned to frequencies higher than 7 kHz±0.3 octave (A) or lower than 7 kHz±0.3 octave (B) were not significantly different between groups. Values are means ± SEM. * p<0.05. Calibration bar = 1 mm.</p