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Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

Little CS, Joyce TA, Hammond CJ, Matta H, Cahn D, Appelt DM, Balin BJ - Front Aging Neurosci (2014)

Bottom Line: The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months.Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41.These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine Philadelphia, PA USA ; Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine Philadelphia, PA, USA.

ABSTRACT
Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

No MeSH data available.


Related in: MedlinePlus

Beta amyloid Aβ 1–42 deposits in the CNS at 2 months pi following intranasal infection with Chlamydia pneumoniae AR-39. Brains were examined by light microscopy for the presence of Aβ 1–42 using a specific anti-Aβ 1–42 antibody. (A–E) Representative images of Aβ 1–42-specific labeling (arrowheads) are shown within different regions of this brain section. Ect (entorhinal cortex), L Ent (lateral entorhinal cortex), Th (thalamus), Prh (perirhinal cortex), Cp (cerebral peduncle). Mag bars (A) = 100μm; (B–E) = 20 μm.
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Figure 4: Beta amyloid Aβ 1–42 deposits in the CNS at 2 months pi following intranasal infection with Chlamydia pneumoniae AR-39. Brains were examined by light microscopy for the presence of Aβ 1–42 using a specific anti-Aβ 1–42 antibody. (A–E) Representative images of Aβ 1–42-specific labeling (arrowheads) are shown within different regions of this brain section. Ect (entorhinal cortex), L Ent (lateral entorhinal cortex), Th (thalamus), Prh (perirhinal cortex), Cp (cerebral peduncle). Mag bars (A) = 100μm; (B–E) = 20 μm.

Mentions: Quantitative analysis of amyloid burden revealed the highest number of Aβ 1–42 immunoreactive deposits (43) at 2 months pi 3.8 mm caudal to bregma, similar to Cpn immunoreactivity at 1 month pi (Table 1A). Overall Aβ 1–42 immunoreactivity was greatest at 2 months pi, having been minimal at 1 month pi and decreasing at 3 and 4 months pi. As noted above, these sections contain the Ect, Prh, cerebral peduncle (Cp), hippocampus, and amygdala, all regions affected in AD (see Figure 4 for Aβ 1–42 immunoreactive deposits). A low but detectable number of amyloid-specific immunoreactive sites were detected within mock-infected control mouse brain tissue at 2, 3, and 4 months pi with an average number of 0.17/section analyzed. The mean number of immunoreactive sites identified was 3.38/mouse ± 2.28 and based upon the results of the student t-test a statistically significant difference (p < 0.05) was observed between experimentally infected tissue and mock-infected control mouse tissue at 2 months pi (60/mouse ± 8) and 3 months pi (17.67 ± 0.67). No statistically significant difference was detected at 1 month pi (3.33 ± 1.17) or 4 months pi (21.83 ± 19.08; Table 1B).


Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

Little CS, Joyce TA, Hammond CJ, Matta H, Cahn D, Appelt DM, Balin BJ - Front Aging Neurosci (2014)

Beta amyloid Aβ 1–42 deposits in the CNS at 2 months pi following intranasal infection with Chlamydia pneumoniae AR-39. Brains were examined by light microscopy for the presence of Aβ 1–42 using a specific anti-Aβ 1–42 antibody. (A–E) Representative images of Aβ 1–42-specific labeling (arrowheads) are shown within different regions of this brain section. Ect (entorhinal cortex), L Ent (lateral entorhinal cortex), Th (thalamus), Prh (perirhinal cortex), Cp (cerebral peduncle). Mag bars (A) = 100μm; (B–E) = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257355&req=5

Figure 4: Beta amyloid Aβ 1–42 deposits in the CNS at 2 months pi following intranasal infection with Chlamydia pneumoniae AR-39. Brains were examined by light microscopy for the presence of Aβ 1–42 using a specific anti-Aβ 1–42 antibody. (A–E) Representative images of Aβ 1–42-specific labeling (arrowheads) are shown within different regions of this brain section. Ect (entorhinal cortex), L Ent (lateral entorhinal cortex), Th (thalamus), Prh (perirhinal cortex), Cp (cerebral peduncle). Mag bars (A) = 100μm; (B–E) = 20 μm.
Mentions: Quantitative analysis of amyloid burden revealed the highest number of Aβ 1–42 immunoreactive deposits (43) at 2 months pi 3.8 mm caudal to bregma, similar to Cpn immunoreactivity at 1 month pi (Table 1A). Overall Aβ 1–42 immunoreactivity was greatest at 2 months pi, having been minimal at 1 month pi and decreasing at 3 and 4 months pi. As noted above, these sections contain the Ect, Prh, cerebral peduncle (Cp), hippocampus, and amygdala, all regions affected in AD (see Figure 4 for Aβ 1–42 immunoreactive deposits). A low but detectable number of amyloid-specific immunoreactive sites were detected within mock-infected control mouse brain tissue at 2, 3, and 4 months pi with an average number of 0.17/section analyzed. The mean number of immunoreactive sites identified was 3.38/mouse ± 2.28 and based upon the results of the student t-test a statistically significant difference (p < 0.05) was observed between experimentally infected tissue and mock-infected control mouse tissue at 2 months pi (60/mouse ± 8) and 3 months pi (17.67 ± 0.67). No statistically significant difference was detected at 1 month pi (3.33 ± 1.17) or 4 months pi (21.83 ± 19.08; Table 1B).

Bottom Line: The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months.Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41.These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine Philadelphia, PA USA ; Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine Philadelphia, PA, USA.

ABSTRACT
Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

No MeSH data available.


Related in: MedlinePlus