Depression Treatment: Inflammation Subverts Hippocampal Synaptic Plasticity in Experimental Multiple Sclerosis.

Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

Filed under: Depression Treatment

PLoS One. 2013; 8(1): e54666
Nisticò R, Mango D, Mandolesi G, Piccinin S, Berretta N, Pignatelli M, Feligioni M, Musella A, Gentile A, Mori F, Bernardi G, Nicoletti F, Mercuri NB, Centonze D

Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1? (IL-1?) perfusion, and both EAE and IL-1? inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1? expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1? signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.
HubMed – depression


Synaptic depression in the CA1 region of freely behaving mice is highly dependent on afferent stimulation parameters.

Filed under: Depression Treatment

Front Integr Neurosci. 2013; 7: 1
Goh JJ, Manahan-Vaughan D

Persistent synaptic plasticity has been subjected to intense study in the decades since it was first described. Occurring in the form of long-term potentiation (LTP) and long-term depression (LTD), it shares many cellular and molecular properties with hippocampus-dependent forms of persistent memory. Recent reports of both LTP and LTD occurring endogenously under specific learning conditions provide further support that these forms of synaptic plasticity may comprise the cellular correlates of memory. Most studies of synaptic plasticity are performed using in vitro or in vivo preparations where patterned electrical stimulation of afferent fibers is implemented to induce changes in synaptic strength. This strategy has proven very effective in inducing LTP, even under in vivo conditions. LTD in vivo has proven more elusive: although LTD occurs endogenously under specific learning conditions in both rats and mice, its induction has not been successfully demonstrated with afferent electrical stimulation alone. In this study we screened a large spectrum of protocols that are known to induce LTD either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo. Low frequency stimulation at 1, 2, 3, 5, 7, or 10 Hz given in the range of 100 through 1800 pulses produced, at best, short-term depression (STD) that lasted for up to 60 min. Varying the administration pattern of the stimuli (e.g., 900 pulses given twice at 5 min intervals), or changing the stimulation intensity did not improve the persistency of synaptic depression. LTD that lasts for at least 24 h occurs under learning conditions in mice. We conclude that a coincidence of factors, such as afferent activity together with neuromodulatory inputs, play a decisive role in the enablement of LTD under more naturalistic (e.g., learning) conditions.
HubMed – depression


Health care costs before and after diagnosis of depression in patients with unexplained pain: a retrospective cohort study using the United Kingdom General Practice Research Database.

Filed under: Depression Treatment

Clinicoecon Outcomes Res. 2013; 5: 37-47
Reed C, Hong J, Novick D, Lenox-Smith A, Happich M

To assess the impact of pain severity and time to diagnosis of depression on health care costs for primary care patients with pre-existing unexplained pain symptoms who subsequently received a diagnosis of depression.This retrospective cohort study analyzed 4000 adults with unexplained pain (defined as painful physical symptoms [PPS] without any probable organic cause) and a subsequent diagnosis of depression, identified from the UK General Practice Research Database using diagnostic codes. Patients were categorized into four groups based on pain severity (milder or more severe; based on number of pain-relief medications and use of opioids) and time to diagnosis of depression (?1 year or>1 year from PPS index date). Annual health care costs were calculated (2009 values) and included general practitioner (GP) consultations, secondary care referrals, and prescriptions for pain-relief medications for the 12 months before depression diagnosis and in the subsequent 2 years. Multivariate models of cost included time period as a main independent variable, and adjusted for age, gender, and comorbidities.Total annual health care costs before and after depression diagnosis for the four patient groups were higher for the groups with more severe pain (£819-£988 versus £565-£628; P < 0.001 for all pairwise comparisons) and highest for the group with more severe pain and longer time to depression diagnosis in the subsequent 2 years (P < 0.05). Total GP costs were highest in the group with more severe pain and longer time to depression diagnosis both before and after depression diagnosis (P < 0.05). In the second year following depression diagnosis, this group also had the highest secondary care referral costs (P < 0.01). The highest drug costs were in the groups with more severe pain (P < 0.001), although costs within each group were similar before and after depression diagnosis.Among patients with unexplained pain symptoms, significant pain in combination with longer time from pain symptoms to depression diagnosis contribute to higher costs for the UK health care system. HubMed – depression


Treatment of Depression in Children & Adolescents by Callahan, Connie

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