To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Examining neurometabolic abnormalities in critical brain areas in schizophrenia and major depressive disorder (MDD) may help guide future pharmacological interventions including glutamate-modulating treatments.
To measure metabolite concentrations within the anterior cingulate cortex (ACC) and thalamus of people with schizophrenia and people with MDD.
Spectra were acquired from 16 volunteers with schizophrenia, 17 with MDD and 18 healthy controls using magnetic resonance spectroscopy on a 7 Tesla scanner.
In the thalamus, there were lower glycine concentrations in the schizophrenia group relative to control (P=0.017) and MDD groups (P=0.012), and higher glutamine concentrations relative to healthy controls (P=0.009). In the thalamus and the ACC, the MDD group had lower myo-inositol concentrations than the control (P=0.014, P=0.009, respectively) and schizophrenia (P=0.004, P=0.002, respectively) groups.
These results support the glutamatergic theory of schizophrenia and indicate a potential glycine deficiency in the thalamus. In addition, reduced myo-inositol concentrations in MDD suggest its involvement in the disorder.
Thalamic glutamine loss and grey matter reduction suggest
neurodegeneration in first-episode schizophrenia, but the duration is
To observe glutamine and glutamate levels, grey matter volumes and social
functioning in patients with schizophrenia followed to 80 months after
Grey matter volumes and proton magnetic resonance spectroscopy
metabolites in left anterior cingulate and left thalamus were measured in
17 patients with schizophrenia before medication and 10 and 80 months
after diagnosis. Social functioning was assessed with the Life Skills
Profile Rating Scale (LSPRS) at 80 months.
The sum of thalamic glutamate and glutamine levels decreased over 80
months, and correlated inversely with the LSPRS. Thalamic glutamine and
grey matter loss were significantly correlated in frontal, parietal,
temporal and limbic regions.
Brain metabolite loss is correlated with deteriorated social functioning
and grey matter losses in schizophrenia, consistent with
Folding variants of α-lactalbumin (α-la) are known to induce cell death in a number of cell types, including mammary epithelial cells (MEC). The native conformation of α-la however has not been observed to exhibit this biological activity. Here we report that native bovine α-la reduced the viability of primary bovine mammary epithelial cells (BMEC) and induced caspase activity in mammospheres, which are alveolar-like structures formed by culturing primary BMEC on extracellular matrix in the presence of lactogenic hormones. These observations suggest a possible role for bovine α-la in involution and/or maintaining the luminal space in mammary alveoli during lactation. In addition, co-incubation of bovine α-la in an in-vitro mammosphere model resulted in decreased β-casein mRNA expression and increased αs1- and κ-casein mRNA expression. This differential effect on casein expression levels is unusual and raises the possibility of manipulating expression levels of individual caseins to alter dairy processing properties. Manipulation of α-la levels could be further investigated for its potential to enhance milk protein expression and/or improve lactational persistency by influencing the balance between proliferation and apoptosis of BMEC, which has a major influence on the milk-producing capacity of the mammary gland.
The concentration of lactoferrin (LTF) in milk varies during lactation, rising sharply during involution. We proposed that LTF might have a regulatory role in involution and investigated its effects in vitro on the viability of bovine mammary epithelial cells (BMEC) and on casein expression in bovine mammospheres. Mammospheres capable of milk protein expression were formed by culturing primary BMEC on extracellular matrix in the presence of lactogenic hormones. Exogenously added LTF decreased β-casein and κ-casein mRNA expression in mammospheres while transfection of a short interfering RNA (siRNA) to suppress LTF expression resulted in increased casein mRNA expression. We believe that LTF exerts its effect on casein gene expression by up-regulating interleukin-1β (IL-1β) as IL-Iβ gene expression was elevated in mammospheres treated with LTF. LTF also decreased viability of BMEC grown as monolayers and as mammospheres. Interestingly, LTF was only effective in reducing casein mRNA expression and viability in mammospheres when added at concentrations found during early involution but was inactive when used at concentrations found in milk. We suggest that LTF has a regulatory role during early involution, decreasing casein expression and reducing BMEC viability.
Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors.
To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness.
Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart.
Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss.
Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.
Membrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.
Using improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.
Brain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.
People with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.
The increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.
Membrane phospholipid abnormalities in people with schizophrenia, measured with 31P magnetic resonance spectroscopy (31P-MRS), have been previously reported in brain regions involved in this disorder.
In this 4.0 Tesla 31P-MRS study of people with schizophrenia, membrane phospholipid metabolism was examined in brain regions previously inaccessible due to their small volumes.
Three-dimensional chemical-shift imaging (3D–CSI) examined 15 cc volumes in 12 brain regions in 11 people with chronic schizophrenia and 11 healthy control volunteers.
Glycerophosphoethanolamine was decreased in the anterior cingulate, right prefrontal cortex and left thalamus, but increased in the left hippocampus and cerebellum in those with schizophrenia. Phosphoethanolamine and glycerophosphocholine were decreased in the right prefrontal region and phosphocholine was decreased in the anterior cingulate. No significant difference in membrane phospholipid levels existed between groups in the parieto-occipital and posterior cingulate regions.
Altered membrane phospholipid metabolism was demonstrated in all regions implicated in schizophrenia.
Thirty schizophrenic patients (20 medicated, 10 off medication) were compared with 30 normal control subjects matched for age, sex, handedness, and intelligence. During the performance of left-hemisphere cognitive activation tasks, normal subjects had significantly increased EEG alpha coherence in areas related to left focal frontal sites, with decreases in temporal and posterior areas. Schizophrenic patients did not show the same degree of focal activation of left frontal areas. During the performance of right-hemisphere cognitive activation tasks, normal subjects and schizophrenic patients had similar patterns of right posterior increases in alpha coherence. Discriminant analyses were able to classify 81.4% of all subjects correctly. It is suggested that the findings indicate an aberrant functional organisation of the brain in schizophrenia, particularly affecting the left hemisphere.
Email your librarian or administrator to recommend adding this to your organisation's collection.